Process for producing 5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxylic acid

ABSTRACT

5-Methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxylic acid of formula (5) or a salt thereof, 
     
       
         
         
             
             
         
       
         
         
           
             is prepared by reacting reacting 2-bromo-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine of formula (3) or a salt thereof, 
           
         
       
    
     
       
         
         
             
             
         
       
         
         
           
             with a metal cyanide, to obtain 2-cyano-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine of formula (4) or a salt thereof, 
           
         
       
    
     
       
         
         
             
             
         
       
         
         
           
             and hydrolyzing the 2-cyano-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine of formula (4) or a salt thereof.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation application of prior U.S. applicationSer. No. 12/631,002, filed Dec. 4, 2009, now U.S. Pat. No. 7,880,005,which is a continuation of prior U.S. application Ser. No. 12/418,750,filed Apr. 6, 2009, now U.S. Pat. No. 7,678,910, the disclosures ofwhich are incorporated herein by reference in their entireties. U.S.application Ser. No. 12/418,750 is a divisional application of priorU.S. application Ser. No. 10/578,844, filed May 10, 2006, now U.S. Pat.No. 7,547,786, which is the National Stage of PCT/JP 04/16874, filedNov. 12, 2004, the disclosures of which are incorporated herein byreference in their entireties. The parent applications claim priority toJapanese Application Nos. 2003-382382, filed Nov. 12, 2003, JP2003-382383, filed Nov. 12, 2003, and JP 2003-382384, filed Nov. 12,2003, the disclosures of which are incorporated herein by reference intheir entireties.

BACKGROUND OF THE INVENTION

1. Technical Field

The present invention relates to a process for producing intermediatesof a useful compound which exhibits an inhibitory action on an activatedcoagulation factor X, and which is thus useful as apreventive/therapeutic drug for thrombus-related diseases.

2. Description of the Background

Compounds having a heterocyclic group and a diamine structure are knownto be useful as preventive/therapeutic drugs for a variety ofthrombus-related diseases, because they exhibit excellent inhibitoryaction against an activated coagulation factor (FXa) (Patent Documents 1to 6, and others). For introducing a heterocyclic group into any of theabove compounds, the compound of formula (5); i.e.,5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxylic acid(hereinafter referred to as compound (5)):

is an important intermediate.

In one process which has hitherto been known to produce compound (5), apiperidone derivative is treated with phosphorus sulfide to thereby forma thiazole ring, and then, a methyl group is introduced to the5-position by use of lithium aluminum hydride, and the 2-position isconverted to a lithium salt of carboxylic acid (see, for example, PatentDocument 7). In another known process, a mercapto group which has beenintroduced into a protected aminopyridine is subjected to a ringformation reaction, followed by chemical reduction of the pyridine ringto thereby form a lithium salt of carboxylic acid (see, for example,Patent Document 1). In yet another known process, protected piperidoneis first transformed into2-amino-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine (hereinafter referredto as compound (2)) in the presence of a secondary amine by use ofsulfur powder and cyanamide, then brominated with copper bromide(II) andalkyl nitrite, after which a methyl group is introduced to the5-position by use of formaldehyde and triacetoxysodium borohydride, andthe resultant 2-bromo-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine(hereinafter referred to as compound (3)) is transformed to a lithiumsalt of carboxylic acid (see, for example, Patent Document 1).

However, any of the above methods involves reactions that are difficultto manipulate when performed on an industrial scale, and includes aconsiderable number of steps because protection/deprotection steps areneeded. Moreover, since chromatography is employed for purification, theoverall production time is extended, which is industriallydisadvantageous. Also, a compound (5) isolated as a lithium salt ishighly hygroscopic, and therefore handling is difficult. Moreover, sincethe compound (5) lacks stability, storage-related problems arise.

In the meantime, compound (2) has been known to be obtained by reacting1-methyl-4-piperidone (hereinafter referred to as compound (1)) withbromine (see for example, Patent Document 8).

However, use of bromine is industrially disadvantageous, as it isdifficult to handle and places a great load on the environment.Moreover, during the process, a brominated compound must be isolated asan intermediate, which means that the process requires two steps.

Another method which has been known for preparing a compound (3)includes bromination of compound (2) with copper bromide (II) (see, forexample, Patent Document 9). However, this method requires copperbromide (II) in an amount equal to or more than that of the compound(2). This makes it difficult to separate by-produced copper salts afterthe reaction, and chromatography is needed for purifying compound (3).Thus, the method is industrially disadvantageous.

-   [Patent Document 1] International Publication WO 01/74774 pamphlet-   [Patent Document 2] International Publication WO 03/000680 pamphlet-   [Patent Document 3] International Publication WO 03/016302 pamphlet-   [Patent Document 4] International Publication WO 2004/058715    pamphlet-   [Patent Document 5] International Publication WO 2004/058728    pamphlet-   [Patent Document 6] International Publication WO 03/000657 pamphlet-   [Patent Document 7] International Publication WO 01/62763 pamphlet-   [Patent Document 8] Netherlands patent No. 6610324-   [Patent Document 9] International Publication WO 92/07849 pamphlet

SUMMARY OF THE INVENTION Problems to be Solved by the Invention

The object of the present invention is to provide a process forindustrially producing, through use of inexpensive starting materials,intermediates of a useful compound which exhibits activated bloodcoagulation factor X inhibitory effect. The process enables efficientproduction of the intermediates with a fewer number of production steps.

Means for Solving the Problems

In order to solve the aforementioned problems, the present inventorshave studied extensively and have found that (a) a compound (5) canefficiently be produced by subjecting a compound (3) to cyanationthereby giving2-cyano-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine (compound(4)) and then hydrolyzing the compound (4); (b) the compound (5) can beproduced by subjecting a compound (2) to reduction and thereby giving4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine (compound 6) and thensubjecting the compound (6) to trihalogenoacetylation and then tohydrolysis; and (c) the compound (2) can conveniently be produced from acompound (1) with a single step by use of a catalytic amount of asecondary amine, the compound (3) can be produced from the compound (2)without copper bromide (II), and each of the compounds (2) to (6) can beisolated, by treating with an acidic compound, as a stable salt with theacidic compound; and that, through use of any of these steps incombination, the compound (5) can be produced in an industrial scalewith a small number of production steps. The present invention isaccomplished based on the findings.

Accordingly, the present invention provides a process for producing acompound represented by formula (5) or a salt thereof:

wherein the process is characterized by comprising reacting a compoundrepresented by formula (3) or a salt thereof:

with a metal cyanide, to thereby obtain a compound represented byformula (4) or a salt thereof:

and hydrolyzing the obtained compound or a salt thereof.

The present invention also provides a process for producing a compoundrepresented by formula (4) or a salt thereof:

wherein the process is characterized by comprising reacting a compoundrepresented by formula (3) or a salt thereof:

with a metal cyanide.

The present invention also provides a process for producing a compoundrepresented by formula (5) or a salt thereof:

wherein the process is characterized by comprising hydrolyzing acompound represented by formula (4) or a salt thereof.

The present invention also provides a process for producing a compoundrepresented by formula (5) or a salt thereof:

wherein the process is characterized by comprising reacting a compoundrepresented by formula (2) or a salt thereof:

with an alkali metal nitrite in the presence of a reducing agent in anaqueous solution of an acidic compound, to thereby obtain a compoundrepresented by formula (6) or a salt thereof:

and reacting the obtained compound or a salt thereof withtrihalogenoacetyl halide in the presence of a base, followed byhydrolysis.

The present invention also provides a process for producing a compoundrepresented by formula (6) or a salt thereof:

wherein the process is characterized by comprising reacting a compoundrepresented by formula (2) or a salt thereof:

with an alkali metal nitrite in the presence of a reducing agent in anaqueous solution of an acidic compound.

The present invention also provides a process for producing a compoundrepresented by formula (5) or a salt thereof:

wherein the process is characterized by comprising reacting a compoundrepresented by formula (6) or a salt thereof:

with trihalogenoacetyl halide in the presence of a base, followed byhydrolysis.

The present invention also provides a process for producing a compoundrepresented by formula (5) or a salt thereof:

wherein the process is characterized by comprising reacting a compoundrepresented by formula (1) or a salt thereof:

with sulfur powder and cyanamide in the presence of a secondary amine,to thereby obtain a compound represented by formula (2) or a saltthereof:

and reacting the obtained compound or a salt thereof hydrobromic acidand alkali metal nitrite, to thereby obtain a compound represented byformula (3) or a salt thereof:

and reacting the obtained compound or a salt thereof with alkyllithiumand carbon dioxide.

The present invention also provides a process for producing a compoundrepresented by formula (2) or a salt thereof:

wherein the process is characterized by comprising reacting a compoundrepresented by formula (1) or a salt thereof:

with sulfur powder and cyanamide in the presence of a secondary amine.

The present invention also provides a process for producing a compoundrepresented by formula (3) or a salt thereof:

wherein the process is characterized by comprising reacting a compoundrepresented by formula (2) or a salt thereof:

with hydrobromic acid and an alkali metal nitrite.

The present invention also provides a salt formed between an acidiccompound and a compound represented by formula (4).

The present invention also provides a salt formed between an acidiccompound and a compound represented by formula (5).

The present invention also provides a salt formed between an acidiccompound and a compound represented by formula (6).

The present invention also provides a salt formed between an acidiccompound and a compound represented by formula (2).

The present invention also provides a salt formed between an acidiccompound and a compound represented by formula (3).

The present invention also provides a process for producing a compoundrepresented by formula (8) or a salt thereof:

(wherein each of R¹ and R² represents a hydrogen atom, hydroxyl, alkylor alkoxy;

Q¹ represents C1-C8 alkylene, C2-C8 alkenylene, or—(CH₂)_(m)—CH₂-A-CH₂—(CH₂)_(n)— (wherein each of m and n represents 0 oran integer of 1 to 3 and A represents an oxygen atom, a nitrogen atom, asulfur atom, —SO—, —SO₂—, —NH—, —O—NH—, —NH—NH—, —S—NH—, —SO—NH—, orSO₂—NH—);

each of R³ and R⁴, which is a substituent linked to a carbon atom, anitrogen atom, or a sulfur atom forming the Q¹-containing ring,represents a hydrogen atom, hydroxyl, alkyl, alkenyl, alkynyl, a halogenatom, halogenoalkyl, cyano, cyanoalkyl, amino, aminoalkyl,N-alkylaminoalkyl, N,N-dialkylaminoalkyl, acyl, acylalkyl, acylaminowhich may have a substituent, alkoxyimino, hydroxyimino, acylaminoalkyl,alkoxy, alkoxyalkyl, hydroxyalkyl, carboxyl, carboxyalkyl,alkoxycarbonyl, alkoxycarbonylalkyl, alkoxycarbonylalkylamino,carboxyalkylamino, alkoxycarbonylamino, alkoxycarbonylaminoalkyl,carbamoyl, N-alkylcarbamoyl whose alkyl may or may not be substituted,N,N-dialkylcarbamoyl whose alkyl may or may not be substituted,N-alkenylcarbamoyl, N-alkenylcarbamoylalkyl, N-alkenyl-N-alkylcarbamoyl,N-alkenyl-N-alkylcarbamoylalkyl, N-alkoxycarbamoyl,N-alkyl-N-alkoxycarbamoyl, N-alkoxycarbamoylalkyl,N-alkyl-N-alkoxycarbamoylalkyl, carbazoyl which may be substituted by 1to 3 alkyl groups, alkylsulfonyl, alkylsulfonylalkyl, 3- to 6-memberedheterocyclic carbonyl which may have a substituent, carbamoylalkyl,N-alkylcarbamoylalkyl whose alkyl may or may not be substituted,N,N-dialkylcarbamoylalkyl whose alkyl may or may not be substituted,carbamoyloxyalkyl, N-alkylcarbamoyloxyalkyl,N,N-dialkylcarbamoyloxyalkyl, 3- to 6-membered heterocycliccarbonylalkyl which may have a substituent, 3- to 6-memberedheterocyclic carbonyloxyalkyl which may have a substituent, aryl,aralkyl, 3- to 6-membered heterocyclic group which may have asubstituent, 3- to 6-membered heterocyclic alkyl which may have asubstituent, alkylsulfonylamino, arylsulfonylamino,alkylsulfonylaminoalkyl, arylsulfonylaminoalkyl,alkylsulfonylaminocarbonyl, arylsulfonylaminocarbonyl,alkylsulfonylaminocarbonylalkyl, arylsulfonylaminocarbonylalkyl, oxo,carbamoyloxy, aralkyloxy, carboxyalkyloxy, alkoxycarbonylalkyloxy,acyloxy, acyloxyalkyl, arylsulfonyl, alkoxycarbonylalkylsulfonyl,carboxyalkylsulfonyl, alkoxycarbonylacyl, alkoxyalkyloxycarbonyl,hydroxyacyl, alkoxyacyl, halogenoacyl, carboxyacyl, aminoacyl,acyloxyacyl, acyloxyalkylsulfonyl, hydroxyalkylsulfonyl,alkoxyalkylsulfonyl, 3- to 6-membered heterocyclic sulfonyl which mayhave a substituent, 3- to 6-membered heterocyclic oxy which may have asubstituent, N-alkylaminoacyl, N,N-dialkylaminoacyl,N,N-dialkylcarbamoylacyl whose alkyl may or may not be substituted,N,N-dialkylcarbamoylalkylsulfonyl whose alkyl may or may not besubstituted, alkylsulfonylacyl, N-arylcarbamoyl, N-3- to 6-memberedheterocyclic carbamoyl, N-alkyl-N-arylcarbamoyl, N-alkyl-N-3- to6-membered heterocyclic carbamoyl, N-arylcarbamoylalkyl, N-3- to6-membered heterocyclic carbamoylalkyl, N-alkyl-N-arylcarbamoylalkyl,N-alkyl-N-3- to 6-membered heterocyclic carbamoylalkyl,aminocarbothioyl, N-alkylaminocarbothioyl, N,N-dialkylaminocarbothioyl,alkoxyalkyl(thiocarbonyl), alkylthioalkyl, or N-acyl-N-alkylaminoalkyl;when R³ and R⁴ are linked together to form a group, the group representsC1-C5 alkylene, C2-C5 alkenylene, C1-C5 alkylenedioxy, or carbonyldioxy;

Q² represents aryl which may have a substituent, arylalkenyl which mayhave a substituent, arylalkynyl which may have a substituent, heteroarylwhich may have a substituent, heteroarylalkenyl which may have asubstituent, a saturated or unsaturated bicyclic or tricyclic condensedhydrocarbon group which may have a substituent, or a saturated orunsaturated bicyclic or tricyclic condensed heterocyclic group which mayhave a substituent;

T¹ represents carbonyl, sulfonyl, —C(═O)—C(═O)—N(R′)—,—C(═S)—C(═O)—N(R′)—, —C(═O)—C(═S)—N(R′)—, —C(═S)—C(═S)—N(R′)— (whereinR′ represents a hydrogen atom, hydroxyl, alkyl, or alkoxy),—C(═O)-A¹-N(R″)— (wherein A¹ represents an C1-C5 alkylene which may havea substituent and R″ represents a hydrogen atom, hydroxyl, alkyl, oralkoxy), —C(═O)—NH—, —C(═S)—NH—, —C(═O)—NH—NH—, —C(═O)-A²-C(═O)—(wherein A² represents a single bond or C1-C5 alkylene),—C(═O)-A³-C(═O)—NH— (wherein A³ represents C1-C5 alkylene),—C(═O)—C(═NOR^(a))—N(R^(b))—, —C(═S)—C(═NOR^(a))—N(R^(b))— (whereinR^(a) represents a hydrogen atom, alkyl, or alkanoyl and R^(b)represents a hydrogen atom, hydroxyl, alkyl, or alkoxy), —C(═O)—N═N—,—C(═S)—N═N—, —C(═NOR^(C))—C(═O)—N(R^(d))— (wherein R^(C) represents ahydrogen atom, alkyl, alkanoyl, aryl, or aralkyl and R^(d) represents ahydrogen atom, hydroxyl, alkyl, or alkoxy),—C(═N—N(R^(e))(R^(f)))—C(═O)—N(R^(g))— (wherein, each of R^(e) and R^(f)represents a hydrogen atom, alkyl, alkanoyl, or alkyl(thiocarbonyl) andR^(g) represents a hydrogen atom, hydroxyl, alkyl, or alkoxy),—C(═O)—NH—C(═O)—, —C(═S)—NH—C(═O)—, —C(═O)—NH—C(═S)—, —C(═S)—NHC(═S)—,—C(═O)—NH—SO₂—, —SO₂—NH—, —C(═NCN)—NH—C(═O)—, —C(═S)—C(═O)—, orthiocarbonyl), wherein the process is characterized by comprisingreacting a compound which is represented by formula (5) and which isproduced through any of the above processes or a salt thereof:

with diamines represented by formula (7) or a salt thereof:

(wherein R¹, R², R³, R⁴, T¹, Q¹, and Q² have the same meanings asdescribed above).

The present invention also provides a process for producing a compoundrepresented by formula (8) or a salt thereof:

(wherein R¹, R², R³, R⁴, T¹, Q¹, and Q² have the same meanings asdescribed above), wherein the process is characterized by comprisingreacting a compound which is represented by formula (5) and which isproduced through any of the above processes or a salt thereof:

with diamines represented by formula (9) or a salt thereof:

(wherein R^(k) is an amino-group-protective group and R¹, R², R³, R⁴,and Q¹ have the same meanings as described above) to thereby obtain acompound represented by formula (10):

(wherein R¹, R², R³, R⁴, Q¹, and R^(k) have the same meanings asdescribed above), and removing R^(k) from the obtained compound or asalt thereof, to thereby produce a compound represented by formula (11)or a salt thereof:

(wherein R¹, R², R³, R⁴, and Q¹ have the same meanings as describedabove), and reacting the obtained compound or a salt thereof with acompound represented by formula (12) or a salt thereof:[F36]HO-T¹-Q²  (12)(wherein T¹ and Q² have the same meanings as described above).

The present invention also provides a process for producing a compoundrepresented by formula (8′):

(wherein R¹, R³, R⁴, T¹, Q¹, and Q² have the same meanings as describedabove), wherein the process is characterized by comprising reacting acompound which is represented by formula (5) and which is producedthrough any of the above processes or a salt thereof:

with diamines represented by formula (13) or a salt thereof:

(wherein R¹, R³, R⁴, and Q¹ have the same meanings as described above)to thereby obtain a compound represented by formula (14) or a saltthereof:

(wherein R¹, R³, R⁴, and Q¹ have the same meanings as described above),and reducing the obtained compound or a salt thereof, to thereby yield acompound represented by formula (11′) or a salt thereof:

(wherein R¹, R³, R⁴, and Q¹ have the same meanings as described above),and reacting the obtained compound or a salt thereof with a compoundrepresented by formula (12) or a salt thereof:[F42]HO-T¹-Q²  (12)(wherein T¹ and Q² have the same meanings as described above).

Effects of the Invention

The processes of the present invention enable production of a compound(5) in an industrially advantageous manner. Through use of the processesof the present invention, a compound which exhibits excellent FXainhibitory effect and thus is useful as a preventive/therapeutic drugfor thrombotic diseases can be produced in an industrially advantageousmanner.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The processes for producing the compound (5) according to the presentinvention are represented by the following reaction scheme and will nextbe described.

Step (A): 1-Methyl-4-piperidone (1) or a salt thereof is reacted, in thepresence of a secondary amine, with a sulfur powder and a cyanamide, tothereby produce a compound (2) or a salt thereof. The compound (1) maybe prepared through, for example, methylation of 4-piperidone by use ofa conventional method.

The cyanamide is preferably used in an amount of 1 to 2 equivalents,more preferably 1 equivalent on the basis of 1 mole of the compound (1).The sulfur powder is preferably used in an amount of 1 to 2 equivalents,more preferably 1 equivalent on the basis of 1 mole of the compound (1).No particular limitation is imposed on the secondary amine. Examples ofthe secondary amine include diethylamine, diisopropylamine, pyrrolidine,piperidine, and morpholine, with pyrrolidine being preferred. The amountof secondary amine added may be a catalytic amount, preferably 0.01 to1.2 equivalents, more preferably 0.1 to 0.5 equivalents, still morepreferably 0.1 equivalents on the basis of 1 mole of the compound (1).

No particular limitation is imposed on the reaction solvent, so long asthe solvent is inert with respect to the reaction. Examples of thesolvent which may be employed include alcoholic solvents such asmethanol, ethanol, and 2-propanol; ether solvents such as diethyl ether,tetrahydrofuran, and 1,4-dioxane; acetonitrile; and acetic acid alkylester solvents such as ethyl acetate and isopropyl acetate. Among thesesolvents, alcoholic solvents are preferred, with 2-propanol being morepreferred.

The reaction temperature, which differs depending on the solvent to beemployed, typically falls within a range of 0° C. to the boiling pointof the solvent, preferably a range of 45° C. to the boiling point of thesolvent. The reaction is carried out for about 1 to 24 hours, preferablyabout 2 to 5 hours until virtually completion.

The reaction mixture may be directly subjected to filtration to isolatethe compound (2) as crystals. Alternatively, when the compound (2) is tobe isolated in the form of a salt, an acidic compound is added to thereaction mixture. The “acidic compound” refers to a compound which, asitself, is acidic, or which, when being dissolved in water, is acidic.Examples of the acidic compound which may be employed include organiccarboxylic acids such as oxalic acid, acetic acid, benzoic acid,p-nitrobenzoic acid, malic acid, tartaric acid, succinic acid, maleicacid, and fumaric acid; organic sulfonic acids such as p-toluenesulfonicacid, and methanesulfonic acid; and inorganic acids such as hydrochloricacid, hydrobromic acid, sulfuric acid, and phosphoric acid. Among theseacidic compounds, hydrobromic acid is preferred.

Step (B): The compound (2) or a salt thereof is reacted, in the presenceof hydrobromic acid, with an alkali metal nitrite, to thereby give acompound (3) or a salt thereof.

Examples of the alkali metal nitrite which may be employed includesodium nitrite, potassium nitrite, and lithium nitrite, with sodiumnitrite being preferred. The alkali metal nitrite is preferably used inan amount of 1 to 3 equivalents, more preferably 1.5 equivalents on thebasis of 1 mole of the compound (2).

The reaction is performed at a temperature falling within a range of −20to 100° C., preferably −5 to 15° C. for about 1 to 36 hours, preferably3 to 24 hours until virtually completion.

The compound (2) may be isolated through addition of an aqueous solutionof an alkali metal hydroxide (e.g., sodium hydroxide, potassiumhydroxide, or lithium hydroxide) or an alkaline earth metal hydroxide(e.g., calcium hydroxide or barium hydroxide), preferably aqueous sodiumhydroxide, for alkalifying the mixture (about pH 12 to 13); extractionof the mixture through use of a suitable solvent; and evaporation underreduced pressure.

No particular limitation is imposed on the solvent employed forextraction. Examples of the extraction solvent include ether solventssuch as diethyl ether, diisopropyl ether, and methyl tert-butyl ether;aromatic hydrocarbon solvents such as benzene and toluene; and aceticacid alkyl ester solvents such as ethyl acetate and isopropyl acetate.Among these solvents, aromatic hydrocarbon solvents are preferred, withtoluene being more preferred.

The compound (3) may be isolated in the form of a salt throughdissolution in a suitable solvent and treatment with an acidic compound.Examples of the acidic compound include the same compounds as describedabove. Of these, p-toluenesulfonic acid is preferred.

No particular limitation is imposed on the solvent. Examples of thesolvent which may be employed include alcoholic solvents such asmethanol, ethanol, and 2-propanol; ether solvents such as diethyl ether,tetrahydrofuran, and 1,4-dioxane; aromatic hydrocarbon solvents such asbenzene and toluene; acetonitrile; and acetic acid alkyl ester solventssuch as ethyl acetate and isopropyl acetate. Among these solvents,alcoholic solvents are preferred, with methanol being more preferred.

Step (C): The compound (3) or a salt thereof is reacted with a metalcyanide, to thereby give2-cyano-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine (hereinafterreferred to as “compound (4)”) or a salt thereof.

Examples of the metal cyanide include sodium cyanide, potassium cyanide,lithium cyanide, copper cyanide, and zinc cyanide. These metal cyanidesmay be employed in combination of two or more species, and a combinationof sodium cyanide and copper cyanide is preferred. The metal cyanide ispreferably used in an amount of 1 to 3 equivalents, more preferably 1.5equivalents on the basis of 1 mole of the compound (3).

No particular limitation is imposed on the reaction solvent, so long asthe solvent is inert with respect to the reaction. Examples of thereaction solvent include amide solvents such as N,N-dimethylformamideand N,N-dimethylacetamide; aromatic hydrocarbon solvents such as benzeneand toluene; and dimethyl sulfoxide. Of these, N,N-dimethylacetamide ispreferred.

The reaction temperature falls within a range of 0 to 200° C.,preferably 140 to 160° C. The reaction is performed for about 8 to 48hours, preferably 13 to 20 hours until virtually completion.

The thus-obtained compound (4) may be isolated through addition ofaqueous sodium hydrogencarbonate or a similar solution; extraction witha suitable solvent; evaporation under reduced pressure.

No particular limitation is imposed on the extraction solvent. Examplesof the extraction solvent which may be employed include ether solventssuch as diethyl ether, diisopropyl ether, and methyl tert-butyl ether;aromatic hydrocarbon solvents such as benzene and toluene; and aceticacid alkyl ester solvents such as ethyl acetate and isopropyl acetate.Among these solvents, aromatic hydrocarbon solvents are preferred, withtoluene being more preferred.

Alternatively, the compound (4) may be isolated in the form of a salt ofan acidic compound. Examples of the acidic compound include the same asdescribed above. Of these acidic compounds, hydrochloric acid ispreferred.

Step (D): The compound (4) or a salt thereof is hydrolyzed, to therebygive a compound (5) or a salt thereof.

The hydrolysis may be carried out by dissolving the compound (4) in asuitable solvent and treating the solution with an aqueous solution ofan alkali metal hydroxide. Examples of the alkali metal hydroxideinclude sodium hydroxide, lithium hydroxide, and potassium hydroxide,with lithium hydroxide being preferred. Examples of the solvent whichmay be employed include alcoholic solvents such as ethanol, methanol,and 2-propanol, acetone, and acetonitrile, with ethanol being preferred.

The reaction temperature falls within a range of 0° C. to the boilingpoint of the solvent, preferably 40 to 70° C. The reaction is performeduntil virtually completion, for about 1 to 24 hours, preferably 5 to 10hours.

The compound (5) may be isolated in the form of a salt through additionof an acidic compound to the reaction mixture. Examples of the acidiccompound include the same as described above. Of these, hydrochloricacid is preferred.

Step (E): The compound (3) or a salt thereof is reacted with analkyllithium and carbon dioxide gas, to thereby give a compound (5) or asalt thereof.

The reaction consists of two sub-steps. The first sub-step is lithiationthrough use of an alkyllithium. The alkyllithium is used preferably inan amount of 1 to 2 equivalents, more preferably 1 to 1.2 equivalents onthe basis of 1 mole of the compound (3). The alkyllithium is preferablyn-butyllithium. The reaction temperature falls within a range of −78° C.to the boiling point of the solvent, preferably −78 to 0° C. Thereaction is performed for several minutes to 24 hours, preferablyseveral minutes to 2 hours until virtually completion.

The second sub-step is a reaction between the lithium salt obtained inthe first sub-step and carbon dioxide gas. Specifically, carbon dioxideis injected to the reaction mixture obtained through the abovelithiation, or the reaction system is placed in a carbon dioxideatmosphere. The reaction temperature falls within a range of −78° C. tothe boiling point of the solvent, preferably −78 to 0° C. The reactionis performed until virtually completion, for several minutes to 24hours, preferably several minutes to 2 hours. Preferably, in the step(E), the sub-steps are both carried out under nitrogen, argon, or asimilar inert gas.

No particular limitation is imposed on the reaction solvent, so long asthe solvent is inert with respect to reaction. Examples of the reactionsolvent include ether solvents such as methyl tert-butyl ether,diisopropyl ether, tetrahydrofuran, and 1,4-dioxane; linear of cyclicsaturated hydrocarbon solvents such as n-hexane, n-heptane, andcyclohexane; and aromatic hydrocarbon solvents such as benzene andtoluene. Among these solvents, ether solvents are preferred, withtetrahydrofuran being more preferred.

The compound (5) may be isolated in the form of a lithium salt bydirectly subjecting the reaction mixture to filtration. However, alithium salt of the compound (5) is unstable. Therefore, preferably, thelithium salt is transformed into a free carboxylic acid, or,alternatively, a suitable second solvent is added to the resultant freecarboxylic acid, and the solution is treated with an acidic compound, tothereby isolate the compound (5) as a salt. Examples of the acidiccompound include the same as described above, with hydrochloric acidbeing preferred.

No particular limitation is imposed on the second solvent. Examples ofthe second solvent which may be employed include alcoholic solvents suchas methanol, ethanol, and 2-propanol; acetonitrile; and acetic acidalkyl ester solvents such as ethyl acetate and isopropyl acetate. Amongthese solvents, alcoholic solvents are preferred, with methanol beingmore preferred.

Step (F): The compound (2) or a salt thereof is reacted with an alkalimetal nitrite in the presence of a reducing agent in an aqueous solutionof an acidic compound, to thereby give a compound (6) or a salt thereof.

Examples of the acidic compound include the same compounds as describedabove, with sulfuric acid being preferred.

Examples of the reducing agent include hydrogen, sodium borohydride,hypophosphorous acid, and formic acid, with hypophosphorous acid beingpreferred. Examples of the alkali metal nitrite include sodium nitrite,potassium nitrite, and lithium nitrite, with sodium nitrite beingpreferred.

The reducing agent is used preferably in an amount of 1 to 3equivalents, more preferably 2 equivalents on the basis of 1 mole of thecompound (2). The alkali metal nitrite is preferably used in an amountof 1 to 3 equivalents, more preferably 2 equivalents on the basis of 1mole of the compound (2). The reaction is performed at a temperaturefalling within a range of −20 to 50° C., preferably −5 to 15° C., forabout 1 to 36 hours, preferably 2 to 24 hours.

The compound (6) may be isolated through addition of an aqueous solutionof an alkali metal hydroxide (e.g., sodium hydroxide, potassiumhydroxide, lithium hydroxide), preferably an aqueous lithium hydroxidesolution for alkalifying the mixture (pH 12 to 13 or thereabouts);extraction through use of a suitable solvent; and evaporation underreduced pressure.

No particular limitation is imposed on the extraction solvent. Examplesof the extraction solvent which may be employed include ether solventssuch as diethyl ether, diisopropyl ether, and methyl tert-butyl ether;aromatic hydrocarbon solvents such as benzene and toluene; acetic acidalkyl ester solvents such as ethyl acetate and isopropyl acetate; andhalohydrocarbon solvents such as dichloromethane and chloroform. Amongthese solvents, acetic acid alkyl ester solvents and halohydrocarbonsolvents are preferred, with ethyl acetate being more preferred.

Alternatively, the compound (6) may be isolated in the form of a saltthrough addition of an acidic compound in a suitable solvent. Noparticular limitation is imposed on the solvent. Examples of the solventwhich may be employed include alcoholic solvents such as methanol,ethanol, and 2-propanol; ether solvents such as diethyl ether,tetrahydrofuran, and 1,4-dioxane; aromatic hydrocarbon solvents such asbenzene and toluene; acetonitrile; and acetic acid alkyl ester solventssuch as ethyl acetate and isopropyl acetate. Among these solvents,alcoholic solvents are preferred, with 2-propanol being more preferred.

Examples of the acidic compound include the same compound as describedabove, with p-toluenesulfonic acid being preferred.

Step (G): The compound (6) or a salt thereof is reacted with atrihalogenoacetyl halide in the presence of a base, followed byhydrolysis, to thereby give a compound (5) or a salt thereof.

The trihalogenoacetyl halide is preferably used in an amount of 1 to 3equivalents, more preferably 2 equivalents on the basis of 1 mole of thecompound (6). Examples of the trihalogenoacetyl halide includetribromoacetyl chloride and trichloroacetyl chloride, withtrichloroacetyl chloride being preferred. No particular limitation isimposed on the base. Examples of the base which may be employed includetertiary amines such as triethylamine, diisopropylethylamine, andN-methylmorpholine; alkali metal hydroxides such as sodium hydroxide,potassium hydroxide, and lithium hydroxide; and inorganic bases such ascarbonic acid salt and hydrogen carbonic acid salt. Among these bases,tertiary amines are preferred, and triethylamine, diisopropylethylamine,and N-methylmorpholine are more preferred. The base is preferably usedin an amount of 1 to 3 equivalents, more preferably 2 equivalents on thebasis of 1 mole of the compound (6).

No particular limitation is imposed on the reaction solvent. Examples ofthe reaction solvent which may be employed include ether solvents suchas diethyl ether, tetrahydrofuran, and 1,4-dioxane; aromatic hydrocarbonsolvents such as benzene and toluene; amide solvents such asN,N-dimethylformamide and N,N-dimethylacetamide; dimethyl sulfoxide;acetonitrile; and acetic acid alkyl ester solvents such as ethyl acetateand isopropyl acetate. Among these solvents, aromatic hydrocarbonsolvents such as toluene and acetic acid alkyl ester solvents such asethyl acetate and isopropyl acetate are preferred, and toluene, ethylacetate, and isopropyl acetate are more preferred.

The reaction temperature, which differs depending on the solvent to beemployed, typically falls within a range of −78° C. to the boiling pointof solvent, preferably 0° C. to the boiling point of solvent. Thereaction is performed for about 1 to 24 hours, preferably 1 to 5 hoursuntil virtually completion.

The hydrolysis may be continuously performed through addition of anaqueous solution of an alkali metal hydroxide to the reaction mixture.Examples of the alkali metal hydroxide include sodium hydroxide, lithiumhydroxide, and potassium hydroxide, with lithium hydroxide beingpreferred.

The reaction temperature typically falls within a range of −5° C. to theboiling point of the solvent, preferably 0° C. to the boiling point ofthe solvent. The reaction is performed for about 1 to 10 hours,preferably 1 to 5 hours until virtually completion.

After completion of hydrolysis, the organic layer and the aqueous layerare partitioned with each other, whereby the compound (5) is collectedin the aqueous layer, and oil-soluble impurities or other oil-solublesubstances are removed to the organic layer. The thus-collected compound(5) may be isolated in the form of a salt through evaporation of theaqueous layer, addition of a suitable second solvent, and addition of anacidic compound.

No particular limitation is imposed on the second solvent. Examples ofthe second solvent which may be employed include alcoholic solvents suchas methanol, ethanol, and 2-propanol; acetonitrile; and acetic acidalkyl ester solvents such as ethyl acetate and isopropyl acetate. Amongthese solvents, alcoholic solvents are preferred, and methanol isparticularly preferred.

Examples of the acidic compound include the same compounds as describedabove, with hydrochloric acid being preferred.

Next will be described a process for producing, from the compound (5), acompound (8) which is useful as a preventive/therapeutic agent forthrombotic diseases. The compound (8) may be produced from the compound(5) through a process described in International Publication WO2004/058715 pamphlet, or a similar process. A representative processrepresented by the following reaction scheme will next be described:

(wherein R¹, R², R³, R⁴, R^(k), T¹, Q¹, and Q² have the same meanings asdescribed above).

Step (H): The compound (5) or a salt thereof is reacted with a diaminecompound (7) or a salt thereof, to thereby give a compound (8) or a saltthereof.

The compound (5) may be transformed, prior to being subjected to thereaction, to a mixed acid anhydride, an acid halide, or an active ester,according to needs. The transformation reaction may be performed throughuse of a reagent under conditions, the reagent and the conditions beingusually employed in a peptide synthesis. When the compound (5) istransformed to a mixed acid anhydride, for example, the compound (5) maybe reacted with a chloroformate such as ethyl chloroformate or isobutylchloroformate in the presence of a base. When the compound (5) istransformed to an acid halide, the compound (5) may be treated with anacid halide such as thionyl chloride or oxalyl chloride. A variety ofactive esters can be produced. For example, the compound (5) may reactedwith a phenol compound such as p-nitrophenol or withN-hydroxybenzotriazole, N-hydroxysuccinimide, or a similar compoundthrough use of a condensing agent such as N,N′-dicyclohexylcarbodiimideor 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride.Alternatively, an active ester of the compound (5) may be produced,among others, by reacting the compound (5) with pentafluorophenyltrifluoroacetate or a similar compound, by reacting the compound (5)with 1-benzotriazolyloxytripyrrolidinophosphonium hexafluorophosphite,by reacting the compound (5) with diethyl cyanophosphate (the Shioirimethod), or by reacting the compound (5) with triphenylphosphine and2,2′-dipyridyldisulfide (the Mukaiyama method). The thus-obtained mixedacid anhydride, acid halide, or active ester of the compound (5) isreacted with a diamine compound (7) in the presence of a suitable basein an inert solvent at a temperature of −78° C. to 150° C., to therebygive a compound (8).

Specific examples of the base employed in the above-described step (H)include carbonates of alkali metals and alkaline earth metals, alkalimetal alkoxides, alkali metal hydroxides, and hydrides (e.g., sodiumcarbonate, and potassium carbonate, sodium ethoxide, potassium butoxide,sodium hydroxide, potassium hydroxide, sodium hydroxide, and potassiumhydroxide); alkyllithiums such as n-butyl lithium; organometallic basessuch as dialkylamino lithium (e.g., lithium diisopropylamide);bissilylamine organometallic bases such as lithiumbis(trimethylsilyl)amide; and organic bases such as pyridine,2,6-lutidine, collidine, 4-dimethylaminopyridine, triethylamine,N-methylmorpholine, diisopropylethylamine, anddiazabicyclo[5.4.0]undec-7-ene (DBU).

Examples of the inert solvent which is employed in the reaction includehaloalkyl solvents such as dichloromethane, chloroform, and carbontetrachloride; ether solvents such as tetrahydrofuran,1,2-dimethoxyethane, and dioxane; aromatic solvents such as benzene andtoluene; amide solvents such as N,N-dimethylformamide,N,N-dimethylacetamide, and N-methylpyrrolidin-2-one. Additionally, insome cases, there may be employed sulfoxide solvents such as dimethylsulfoxide, and sulfolane; and ketone solvents such as acetone and methylethyl ketone.

Step (I): The compound (5) or a salt thereof is reacted with a diaminecompound (9) or a salt thereof, to thereby give a compound (10) or asalt thereof. Examples of a protection group for the amino group,represented by R^(k), include alkanoyls such as acetyl; alkoxycarbonylssuch as methoxycarbonyl, ethoxycarbonyl, and tert-butoxycarbonyl;arylmethoxycarbonyls such as benzyloxycarbonyl,paramethoxybenzyloxycarbonyl, and p-(or o-)nitrobenzyloxycarbonyl;benzyls; arylmethyls such as triphenylmethyl; aroyl such as benzoyl; andarylsulfonyls such as 2,4-dinitrobenzenesulfonyl andorthonitrobenzenesulfonyl. The reaction of the compound (5) and thediamine compound (9) may be performed in a manner similar to thatdescribed in relation to the step (H).

Step (J): The compound (10) or a salt thereof is deprotected throughremoval of the protection group (R^(k)), to thereby give a compound (11)or a salt thereof. The deprotection reaction may be performed throughuse of a reagent under conditions, the reagent and the conditions beingusually selected in accordance with the type of the protection group.For example, when the protection group is a tert-butoxycarbonyl group,the compound (10) or a salt thereof may be treated at a temperature of−20 to 70° C. with trifluoroacetic acid or a similar substance.

Step (K): The compound (11) or a salt thereof is reacted with a compound(12) or a salt thereof, to thereby give a compound (8) or a saltthereof. The reaction may be performed in a manner similar to thatdescribed above in relation to the step (H).

Step (L): The compound (5) or a salt thereof is reacted with a compound(13) or a salt thereof, to thereby give a compound (14) or a saltthereof. In the reaction, R¹ is preferably a hydrogen atom.

The reaction may be performed in a manner similar to that describedabove in relation to step (I) or (H).

Step (M): The compound (14) or a salt thereof is reduced, to therebygive a compound (11) or a salt thereof in which R² in formula (11) is ahydrogen atom. The reduction may be performed through catalyticreduction in the presence of a catalyst such as platinum or palladiumthrough, if necessary, pressurization.

It should be noted that the starting materials of steps (I) to (M);i.e., the compounds (7), (9), (12), and (13) may be obtained through amethod described in International Publication WO 2004/058715 pamphlet.

Next will be described the substituents of the compound represented byformula (8).

<Group Q²>

Q² means an aryl group which may have a substituent, an arylalkenylgroup which may have a substituent, an arylalkynyl group which may havea substituent, an heteroaryl group which may have a substituent, anheteroarylalkenyl group which may have a substituent, a saturated orunsaturated bicyclic or tricyclic fused hydrocarbon group which may havea substituent, or a saturated or unsaturated bicyclic or tricyclic fusedheterocyclic group which may have a substituent.

In group Q², examples of the aryl group include C6-C14 aryl groups suchas phenyl, naphthyl, anthryl, and phenanthryl. The arylalkenyl is agroup composed of a C6-C14 aryl group and a C2-C6 alkenylene group, andspecific examples include a styryl group. The arylalkynyl group is agroup composed of a C6-C 14 aryl group and a C2-C6 alkynylene group, andspecific examples include a phenylethynyl group.

The heteroaryl group is a monovalent aromatic group having at least oneheteroatom selected from among an oxygen atom, a sulfur atom, and anitrogen atom. Specific examples include heteroaryl groups having atotal number of ring-forming atoms of 5 or 6 such as pyridyl,pyridazinyl, pyrazinyl, furyl, thienyl, pyrrolyl, thiazolyl, oxazolyl,pyrimidinyl, and tetrazolyl. The heteroarylalkenyl group is a groupcomposed of the above heteroaryl group and a C2-C6 alkenylene group, andspecific examples include thienylethenyl and pyridylethenyl.

The saturated or unsaturated bicyclic or tricyclic condensed hydrocarbongroup is a monovalent group derived from saturated or unsaturatedbicyclic or tricyclic condensed hydrocarbon. The saturated orunsaturated bicyclic or tricyclic condensed hydrocarbon is a bicyclic ortricyclic condensed hydrocarbon which is formed through condensation of2 or 3 saturated or unsaturated 5- or 6-membered cyclic hydrocarbonswhich may be identical to or different from one another. Examples of thesaturated or unsaturated 5- or 6-membered cyclic hydrocarbon includecyclopentane, cyclopentene, cyclohexane, cyclohexene, cyclohexadiene,and benzene. Specific examples of the saturated or unsaturated bicyclicor tricyclic condensed hydrocarbon include indenyl, indanyl,tetrahydronaphthyl, and naphthyl. No particular limitation is imposed onthe position, in the saturated or unsaturated bicyclic or tricycliccondensed hydrocarbon group, to which T¹ is linked.

The saturated or unsaturated bicyclic or tricyclic condensedheterocyclic group refers to a monovalent group derived from saturatedor unsaturated bicyclic or tricyclic condensed heterocyclic ring. Theterm “saturated or unsaturated bicyclic or tricyclic condensedheterocyclic ring” refers to any of the following compounds 1) to 3):

1) bicyclic or tricyclic condensed heterocyclic ring which is formedthrough condensation of 2 or 3 saturated or unsaturated 5- to 7-memberedheterocyclic rings which may be identical to or different from oneanother,

2) bicyclic or tricyclic condensed heterocyclic ring which is formedthrough condensation of one saturated or unsaturated 5- to 7-memberedheterocyclic ring and 1 or 2 saturated or unsaturated 5- or 6-memberedcyclic hydrocarbons, and

3) tricyclic condensed heterocyclic ring which is formed throughcondensation of 2 saturated or unsaturated 5- to 7-membered heterocyclicrings and one saturated or unsaturated 5- or 6-membered cyclichydrocarbon.

No particular limitation is imposed on the position, in theaforementioned saturated or unsaturated bicyclic or tricyclic condensedheterocyclic group, to which T¹ is linked.

The aforementioned saturated or unsaturated 5- to 7-memberedheterocyclic ring refers to a heterocyclic ring having at least oneheteroatom selected from an oxygen atom, a sulfur atom, and a nitrogenatom. Specific examples include furan, pyrrole, thiophene, pyrazole,imidazole, oxazole, oxazolidine, thiazole, thiadiazole, furazane, pyran,pyridine, pyrimidine, pyridazine, pyrrolidine, piperazine, piperidine,oxazine, oxadiazine, morpholine, thiazine, thiadiazine, thiomorpholine,tetrazole, triazole, triazine, thiadiazine, oxadiazine, azepine,diazepine, triazepine, thiazepine, and oxazepine. The saturated orunsaturated 5- or 6-membered cyclic hydrocarbon includes the same asexemplified in relation to the saturated or unsaturated bicyclic ortricyclic condensed hydrocarbon group. Specific examples of thesaturated or unsaturated bicyclic or tricyclic condensed heterocyclicgroup include benzofuryl, isobenzofuryl, benzothienyl, indolyl,indolinyl, isoindolyl, isoindolinyl, indazolyl, quinolyl,dihydroquinolyl, 4-oxodihydroquinolyl(dihydroquinolin-4-one),tetrahydroquinolyl, isoquinolyl, tetrahydroisoquinolyl, chromenyl,chromanyl, isochromanyl, 4H-4-oxobenzopyranyl,3,4-dihydro-4H-4-oxobenzopyranyl, 4H-quinoliznyl, quinazolinyl,dihydroquinazolinyl, tetrahydroquinazolinyl, quinoxalinyl,tetrahydroquinoxalinyl, cinnolinyl, tetrahydrocinnolinyl, indolizinyl,tetrahydroindolizinyl, benzothiazolyl, tetrahydrobenzothiazolyl,benzoxazolyl, benzoisothiazolyl, benzoisoxazolyl, benzimidazolyl,naphthyridinyl, tetrahydronaphthyridinyl, thienopyridyl,tetrahydrothienopyridyl, thiazolopyridyl, tetrahydrothiazolopyridyl,thiazolopyridazinyl, tetrahydrothiazolopyridazinyl, pyrrolopyridyl,dihydropyrrolopyridyl, tetrahydropyrrolopyridyl, pyrrolopyrimidinyl,dihydropyrrolopyrimidinyl, pyridoquinazolinyl,dihydropyridoquinazolinyl, pyridopyrimidinyl,tetrahydropyridopyrimidinyl, pyranothiazolyl, dihydropyranothiazolyl,furopyridyl, tetrahydrofuropyridyl, oxazolopyridyl,tetrahydroxazolopyridyl, oxazolopyridazinyl,tetrahydroxazolopyridazinyl, pyrrolothiazolyl, dihydropyrrolothiazolyl,pyrroloxazolyl, dihydropyrroloxazolyl, thienopyrrolyl,thiazolopyrimidinyl, 4-oxotetrahydrocinnolinyl, 1,2,4-benzothiadiazinyl,1,1-dioxy-2H-1,2,4-benzothiadiazinyl, 1,2,4-benzoxadiazinyl,cyclopentapyranyl, thienofuranyl, furopyranyl, pyridoxazinyl,pyrazoloxazolyl, imidazothiazolyl, imidazopyridyl,tetrahydroimidazopyridyl, pyrazinopyridazinyl, benzisoquinolyl,furocinnolyl, pyrazolothiazolopyridazinyl,tetrahydropyrazolothiazolopyridazinyl,hexahydrothiazolopyridazinopyridazinyl, imidazotriazinyl,oxazolopyridyl, benzoxepynyl, benzazepinyl, tetrahydrobenzazepinyl,benzodiazepinyl, benzotriazepinyl, thienoazepinyl,tetrahydrothienoazepinyl, thienodiazepinyl, thienotriazepinyl,thiazoloazepinyl, tetrahydrothiazoloazepinyl,4,5,6,7-tetrahydro-5,6-tetramethylenethiazolopyridazinyl, and5,6-trimethylene-4,5,6,7-tetrahydrothiazolopyridazinyl. No particularlimitation is imposed on the manner of the condensation of the abovecondensed heterocyclic group.

Each of the aforementioned aryl, heteroaryl, arylalkenyl,heteroarylalkenyl, a saturated or unsaturated bicyclic or tricycliccondensed hydrocarbon group, and a saturated or unsaturated bicyclic ortricyclic condensed heterocyclic group may have 1 to 3 substituents.Examples of the substituents include hydroxyl, halogen atoms such as afluorine atom, a chlorine atom, a bromine atom, and an iodine atom,C1-C6 halogenoalkyl containing 1 to 3 halogen atoms, amino, cyano,aminoalkyl, nitro, hydroxyalkyl (e.g., hydroxymethyl and2-hydroxyethyl), alkoxyalkyl (e.g., methoxymethyl and 2-methoxyethyl),carboxyl, carboxyalkyl (e.g., carboxymethyl and 2-carboxyethyl),alkoxycarbonylalkyl (e.g., methoxycarbonylmethyl andethoxycarbonylmethyl), acyl (e.g., alkanoyls such as formyl, acetyl, andpropionyl), amidino, hydroxyamidino(amino(hydroxyimino)methyl), linear,branched, or cyclic C1-C6 alkyl (e.g., methyl and ethyl), linear,branched, or cyclic C1-C6 alkoxy (e.g., methoxy and ethoxy), amidinowhich is substituted by linear, branched, or cyclic C1-C6 alkyl (e.g.,imino(methylamino)methyl), amidino which is substituted by a linear,branched, or cyclic C1-C6 alkoxy group (e.g.,amino(methoxyimino)methyl), amidino which is substituted by linear,branched, or cyclic C2-C7 alkoxycarbonyl (e.g.,amino(methoxycarbonylimino)methyl and amino(ethoxycarbonylimino)methyl),linear, branched, or cyclic C2-C6 alkenyl (e.g., vinyl and allyl),linear or branched C2-C6 alkynyl (e.g., ethynyl and propynyl), linear,branched, or cyclic C2-C6 alkoxycarbonyl (e.g., methoxycarbonyl andethoxycarbonyl), carbamoyl, mono or dialkylcarbamoyl which issubstituted by linear, branched, or cyclic C1-C6 alkyl group at thenitrogen atom thereof (e.g., methylcarbamoyl, ethylcarbamoyl,dimethylcarbamoyl, and ethylmethylcarbamoyl), mono or dialkylamino whichis substituted by linear, branched, or cyclic C1-C6 alkyl (e.g.,ethylamino, dimethylamino, and methylethylamino) and 5- or 6-memberednitrogen-containing heterocyclic group (e.g., pyrrolidino, piperidino,piperazino, and morpholino).

Among the above-described groups, group Q² is preferably any one of thefollowing 12 groups (a) to (l);

(wherein each of R⁵ and R⁶ represents a hydrogen atom, cyano, a halogenatom, alkyl, hydroxyalkyl, alkoxy, alkoxyalkyl, carboxyl, carboxyalkyl,acyl, alkoxycarbonyl, alkoxycarbonylalkyl, or phenyl which may besubstituted by cyano, hydroxyl, a halogen atom, alkyl, or alkoxy, andeach of R⁷ and R⁸ represents a hydrogen atom, hydroxyl, nitro, amino,cyano, a halogen atom, alkyl, alkenyl, alkynyl, halogenoalkyl,hydroxyalkyl, alkoxy, alkoxyalkyl, carboxyl, carboxyalkyl, acyl,carbamoyl, N-alkylcarbamoyl, N,N-dialkylcarbamoyl, alkoxycarbonyl,amidino, or alkoxycarbonylalkyl);

(wherein each of R⁹ and R¹⁰ represents a hydrogen atom, hydroxyl, nitro,amino, cyano, a halogen atom, alkyl, alkenyl, alkynyl, halogenoalkyl,hydroxyalkyl, alkoxy, alkoxyalkyl, carboxyl, carboxyalkyl, acyl,carbamoyl, N-alkylcarbamoyl, N,N-dialkylcarbamoyl, alkoxycarbonyl,amidino, or alkoxycarbonylalkyl);

(wherein each of R¹¹, R¹², and R¹³ represents a hydrogen atom, hydroxyl,nitro, amino, cyano, a halogen atom, alkyl, alkenyl, alkynyl,halogenoalkyl, hydroxyalkyl, alkoxy, alkoxyalkyl, carboxyl,carboxyalkyl, acyl, carbamoyl, N-alkylcarbamoyl, N,N-dialkylcarbamoyl,alkoxycarbonyl, amidino, or alkoxycarbonylalkyl);

(wherein X¹ represents CH₂, CH, NH, NOH, N, O, or S, and each of R¹⁴,R¹⁵ and R¹⁶ represents a hydrogen atom, hydroxyl, nitro, amino, cyano, ahalogen atom, alkyl, alkenyl, alkynyl, halogenoalkyl, hydroxyalkyl,alkoxy, alkoxyalkyl, carboxyl, carboxyalkyl, acyl, carbamoyl,N-alkylcarbamoyl, N,N-dialkylcarbamoyl, alkoxycarbonyl, amidino, oralkoxycarbonylalkyl);

(wherein X² represents NH, N, O, or S; X³ represents N, C, or CH; X⁴represents N, C, or CH, and each of R¹⁷ and R¹⁸ represents a hydrogenatom, hydroxyl, nitro, amino, cyano, a halogen atom, alkyl, alkenyl,alkynyl, halogenoalkyl, hydroxyalkyl, alkoxy, alkoxyalkyl, carboxyl,carboxyalkyl, acyl, carbamoyl, N-alkylcarbamoyl, N,N-dialkylcarbamoyl,alkoxycarbonyl, amidino, or alkoxycarbonylalkyl, excluding the caseswhere X³ and X⁴ are combinations of C and CH, and are both C or CH;

(wherein N denotes that one or two ring carbon atoms of the ring havingR¹⁹ and being represented with reference “N” are substituted bynitrogen, each of R¹⁹, R²⁰, and R²¹ represents a hydrogen atom,hydroxyl, nitro, amino, cyano, a halogen atom, alkyl, alkenyl, alkynyl,halogenoalkyl, hydroxyalkyl, alkoxy, alkoxyalkyl, carboxyl,carboxyalkyl, acyl, carbamoyl, N-alkylcarbamoyl, N,N-dialkylcarbamoyl,alkoxycarbonyl, amidino, or alkoxycarbonylalkyl);

(wherein X⁵ represents CH₂, CH, N, or NH; Z¹ represents N, NH, or O; Z²represents CH₂, CH, C, or N; Z³ represents CH₂, CH, S, SO₂, or C═O;X⁵—Z² represents a moiety in which X⁵ and Z² are linked via a singlebond or a double bond; each of R²² and R²³ represents a hydrogen atom,hydroxyl, nitro, amino, cyano, a halogen atom, alkyl, alkenyl, alkynyl,halogenoalkyl, hydroxyalkyl, alkoxy, alkoxyalkyl, carboxyl,carboxyalkyl, acyl, carbamoyl, N-alkylcarbamoyl, N,N-dialkylcarbamoyl,alkoxycarbonyl, amidino, or alkoxycarbonylalkyl; R²⁴ represents ahydrogen atom or alkyl);

(wherein X⁶ represents O or S, and each of R²⁵ and R²⁶ represents ahydrogen atom, hydroxyl, nitro, amino, cyano, a halogen atom, alkyl,alkenyl, alkynyl, halogenoalkyl, hydroxyalkyl, alkoxy, alkoxyalkyl,carboxyl, carboxyalkyl, acyl, carbamoyl, N-alkylcarbamoyl,N,N-dialkylcarbamoyl, alkoxycarbonyl, amidino, or alkoxycarbonylalkyl);

(wherein each of R²⁷ and R²⁸ represents a hydrogen atom, hydroxyl,nitro, amino, cyano, halogen atom, alkyl, alkenyl, alkynyl,halogenoalkyl, hydroxyalkyl, alkoxy, alkoxyalkyl, carboxyl,carboxyalkyl, acyl, carbamoyl, N-alkylcarbamoyl, N,N-dialkylcarbamoyl,alkoxycarbonyl, amidino or alkoxycarbonylalkyl);

(wherein each of E¹ and E² represents N or CH, and each of R²⁹ and R³⁰represents a hydrogen atom, hydroxyl, nitro, amino, cyano, a halogenatom, alkyl, alkenyl, alkynyl, halogenoalkyl, hydroxyalkyl, alkoxy,alkoxyalkyl, carboxyl, carboxyalkyl, acyl, carbamoyl, N-alkylcarbamoyl,N,N-dialkylcarbamoyl, alkoxycarbonyl, amidino, or alkoxycarbonylalkyl);

(wherein Y¹ represents CH or N; Y² represents —N(R³³)— (Wherein R³³represents a hydrogen atom or C1-C6 alkyl.), O, or S, each of R³¹ andR³² represents a hydrogen atom, hydroxyl, nitro, amino, cyano, a halogenatom, alkyl, alkenyl, alkynyl, halogenoalkyl, hydroxyalkyl, alkoxy,alkoxyalkyl, carboxyl, carboxyalkyl, acyl, carbamoyl, N-alkylcarbamoyl,N,N-dialkylcarbamoyl, alkoxycarbonyl, amidino, or alkoxycarbonylalkyl);and

(wherein numerals 1 to 8 indicate positions; each of N indicate that anyone of carbon atoms of positions 1 to 4 and any one of carbon atoms ofpositions 5 to 8 has been substituted by a nitrogen atom; each of R³⁴,R³⁵, and R³⁶ represents a hydrogen atom, hydroxyl, nitro, amino, cyano,a halogen atom, alkyl, alkenyl, alkynyl, halogenoalkyl, hydroxyalkyl,alkoxy, alkoxyalkyl, carboxyl, carboxyalkyl, acyl, carbamoyl,N-alkylcarbamoyl, N,N-dialkylcarbamoyl, alkoxycarbonyl, amidino, oralkoxycarbonylalkyl).

These groups will next be described in detail.

In the description of R⁵ to R³⁶ in the above groups, the halogen atom isa fluorine atom, a chlorine atom, a bromine atom, or an iodine atom; thealkyl is a linear, branched, or cyclic C1-C6; the alkenyl is a linear,branched, or cyclic C2-C6; the alkynyl is a linear or branched C2-C6;the hydroxyalkyl is a group corresponding to the above C₁-C₆ alkyl whichhas been substituted by one hydroxyl group; the alkoxy is a linear,branched, or cyclic C1-C6; the alkoxyalkyl is a group corresponding tothe above C₁-C₆ alkyl which has been substituted by the above oneC₁-C₆alkoxy group; the carboxyalkyl is a group corresponding to theabove C₁-C₆ alkyl which has been substituted by one carboxyl group; theacyl is a C1-C6 alkanoyl (including formyl), aroyl such as benzoyl ornaphthoyl, or arylalkanoyl corresponding to the above C₁-C₆ alkanoylwhich has been substituted by the above C₆-C₁₄ aryl; theN-alkylcarbamoyl is a group corresponding to a carbamoyl group which hasbeen substituted by the above C₁-C₆ alkyl group at the nitrogen atom ofthe carbamoyl group; the N,N-dialkylcarbamoyl is a group correspondingto a carbamoyl group which has been substituted by two of the aboveC₁-C₆ alkyl groups at the nitrogen atom of the carbamoyl group; thealkoxycarbonyl is a group composed of the above C₁-C₆ alkoxy andcarbonyl; the alkoxycarbonylalkyl is a group corresponding to the aboveC₁-C₆ alkyl which has been substituted by one of the (C₁-C₆alkoxy)carbonyl groups mentioned above, the halogenoalkyl is a groupcorresponding to the above C₁-C₆ alkyl which has been substituted by 1to 3 halogen atoms. In the above description, no particular limitationis imposed on the position of the substitution.

In the following group:

(wherein R⁵, R⁶, R⁷, and R⁸ have the same meanings as described above,numerals 1 to 6 represent positions), each of R⁵ and R⁶ is preferably ahydrogen atom, cyano, a halogen atom, alkyl, alkenyl, alkynyl, orhalogenoalkyl, with a hydrogen atom and alkyl being more preferred. Ofalkyl groups, methyl is preferred. Preferably, one of R⁷ and R⁸ is ahydrogen atom, and the other group is a hydrogen atom, cyano, a halogenatom, alkyl, alkenyl, alkynyl, or halogenoalkyl. Among the cases inwhich one of R⁷ and R⁸ is a hydrogen atom, the other group is morepreferably a hydrogen atom, a halogen atom, alkyl, or alkynyl. In thiscase, the halogen atom is preferably a fluorine atom, a chlorine atom,or a bromine atom, and the alkyl group is preferably a methyl group. Asalkynyl, ethynyl is particularly preferred. Preferred examples of thegroups represented by the above formula include chlorostyryl,fluorostyryl, bromostyryl, and ethynylstyryl. No particular limitationis imposed on the position, in any of these groups, to which a halogenatom, alkyl, or alkynyl is linked. Among the positions of the grouprepresented by the above formula, 4-position is particularly preferred.Preferred examples of the groups include 4-chlorostyryl, 4-fluorostyryl,4-bromostyryl, and 4-ethynylstyryl.

In the following group:

(wherein R⁹ and R¹⁰ have the same meanings as described above, andnumerals “1” to “6” represent positions), each of R⁹ and R¹⁰ ispreferably a hydrogen atom, a halogen atom, alkyl, or alkynyl. The casewhere R⁹ is a hydrogen atom and R¹⁰ is a hydrogen atom, a halogen atom,alkyl, or alkynyl is more preferred. In the above case, the halogen atomis preferably fluorine, chlorine, or bromine, the alkyl group ispreferably methyl, and the alkynyl group is particularly preferablyethynyl. Preferred examples of the group represented by the aboveformula include chlorophenylethynyl, fluorophenylethynyl,bromophenylethynyl, and ethynylphenylethynyl. No limitation is imposedon the position, in any of these groups, to which a halogen atom, alkyl,or alkynyl is linked. Among them, 4-position is particularly preferred.Specifically, 4-chlorophenylethynyl, 4-fluorophenylethynyl,4-bromophenylethynyl, and 4-ethynylphenylethynyl are preferred, amongothers.

In the following group:

(wherein R¹¹, R¹², and R¹³ have the same meanings as described above,and numerals “1” to “8” represent positions) each of R¹¹, R¹² and R¹³ ispreferably a hydrogen atom, cyano, a halogen atom, alkyl, alkenyl,alkynyl, or halogenoalkyl. R¹¹ is preferably a hydrogen atom, alkyl, ahalogen atom, or hydroxyl, with a hydrogen atom being more preferred.Preferably, one of R¹² and R¹³ is a hydrogen atom, and the other groupis a hydrogen atom, cyano, a halogen atom, alkyl, alkenyl, alkynyl, orhalogenoalkyl. Among the cases in which one of R¹² and R¹³ is a hydrogenatom, the other group is more preferably a hydrogen atom, a halogenatom, alkyl, or alkynyl. In this case, the halogen atom is preferably afluorine atom, a chlorine atom, or a bromine atom, and the alkyl groupis preferably a methyl group. As alkynyl, ethynyl is preferred. In thenaphthyl group, a 2-naphthyl group is preferred to a 1-naphthyl group.In the case of the 2-naphthyl group, the position substituted by ahalogen atom, alkyl group or alkynyl group is preferably a 6- or7-position in the above formula though it should not be particularlylimited, with a 6-position being most preferred. These naphthyl groupsare preferably substituted by a chlorine, fluorine, or bromine atom, analkynyl group, or the like. Particularly preferably, these naphthylgroups are substituted with a chlorine, fluorine, or bromine atom, analkynyl group, or the like. Specific examples include6-chloro-2-naphthyl, 6-fluoro-2-naphthyl, 6-bromo-2-naphthyl,6-ethynyl-2-naphthyl, 7-chloro-2-naphthyl, 7-fluoro-2-naphthyl,7-bromo-2-naphthyl, and 7-ethynyl-2-naphthyl.

In the following group:

(wherein X¹, R¹⁴, R¹⁵, and R¹⁶ have the same meanings as describedabove, and numerals “4” to “7” represent positions), X¹ is preferablyNH, NOH, N, O, or S, with NH, O, and S being more preferred. R¹⁴ ispreferably a hydrogen atom, a halogen atom, acyl, N-alkylcarbamoyl,N,N-dialkylcarbamoyl, or alkyl. Each of R¹⁵ and R¹⁶ is preferably ahydrogen atom, cyano, a halogen atom, alkyl, alkenyl, alkynyl, orhalogenoalkyl. Preferably, one of R¹⁵ and R¹⁶ is a hydrogen atom or ahalogen atom, with a fluorine atom or a chlorine atom being morepreferred, and the other group is a hydrogen atom, cyano, a halogenatom, alkyl, alkenyl, alkynyl, or halogenoalkyl. Among them, the othergroup is particularly preferably a hydrogen atom, a halogen atom, alkyl,or alkynyl. In this case, the halogen atom is preferably a fluorineatom, a chlorine atom, or a bromine atom, the alkyl group is preferablymethyl, and the alkynyl group is preferably ethynyl. No particularlimitation is imposed on the position to which a halogen atom, alkyl, oralkynyl is linked. Among them, 4-, 5-, and 6-positions are preferred.

Preferred examples of the group represented by the above formula include5-chloroindolyl, 5-fluoroindolyl, 5-bromoindolyl, 5-ethynylindolyl,5-methylindolyl, 5-chloro-4-fluoroindolyl, 5-chloro-3-fluoroindolyl,5-fluoro-3-chloroindolyl, 5-ethynyl-3-fluoroindolyl,5-chloro-3-(N,N-dimethylcarbamoyl)indolyl,5-fluoro-3-(N,N-dimethylcarbamoyl)indolyl, 5-chloro-3-formylimidolyl,5-fluoro-3-formylindolyl, 6-chloroindolyl, 6-fluoroindolyl,6-bromoindolyl, 6-ethynylindolyl, 6-methylindolyl, 5-chlorobenzothienyl,5-fluorobenzothienyl, 5-bromobenzothienyl, 5-ethynylbenzothienyl,5-methylbenzothienyl, 5-chloro-4-fluorobenzothienyl,6-chlorobenzothienyl, 6-fluorobenzothienyl, 6-bromobenzothienyl,6-ethynylbenzothienyl, 6-methylbenzothienyl, 5-chlorobenzofuryl,5-fluorobenzofuryl, 5-bromobenzofuryl, 5-ethynylbenzofuryl,5-methylbenzofuryl, 5-chloro-4-fluorobenzofuryl, 6-chlorobenzofuryl,6-fluorobenzofuryl, 6-bromobenzofuryl, 6-ethynylbenzofuryl, and6-methylbenzofuryl.

No particular limitation is imposed on the position, in any of thesesubstituents, to which T¹ is linked. In the above formula (d),2-position and 3-position are preferred. Preferably, the group is, amongothers, 5-chloroindol-2-yl, 5-fluoroindol-2-yl, 5-bromoindol-2-yl,5-ethynylindol-2-yl, 5-methylindol-2-yl, 5-chloro-4-fluoroindol-2-yl,5-chloro-3-fluoroindol-2-yl, 3-bromo-5-chloroindol-2-yl,3-chloro-5-fluoroindol-2-yl, 3-bromo-5-fluoroindol-2-yl,5-bromo-3-chloroindol-2-yl, 5-bromo-3-fluoroindol-2-yl,5-chloro-3-formylindol-2-yl, 5-fluoro-3-formylindol-2-yl,5-bromo-3-formylindol-2-yl, 5-ethynyl-3-formylindol-2-yl,5-chloro-3-(N,N-dimethylcarbamoyl)indol-2-yl,5-fluoro-3-(N,N-dimethylcarbamoyl)indol-2-yl,5-bromo-3-(N,N-dimethylcarbamoyl)indol-2-yl,5-ethynyl-3-(N,N-dimethylcarbamoyl)indol-2-yl, 6-chloroindol-2-yl,6-fluoroindol-2-yl, 6-bromoindol-2-yl, 6-ethynylindol-2-yl,6-methylindol-2-yl, 5-chloroindol-3-yl, 5-fluoroindol-3-yl,5-bromoindol-3-yl, 5-ethynylindol-3-yl, 5-methylindol-3-yl,5-chloro-4-fluoroindol-3-yl, 6-chloroindol-3-yl, 6-fluoroindol-3-yl,6-bromoindol-3-yl, 6-ethynylindol-3-yl, 6-methylindol-3-yl,5-chlorobenzothiophen-2-yl, 5-fluorobenzothiophen-2-yl,5-bromobenzothiophen-2-yl, 5-ethynylbenzothiophen-2-yl,5-methylbenzothiophen-2-yl, 5-chloro-4-fluorobenzothiophen-2-yl,6-chlorobenzothiophen-2-yl, 6-fluorobenzothiophen-2-yl,6-bromobenzothiophen-2-yl, 6-ethynylbenzothiophen-2-yl,6-methylbenzothiophen-2-yl, 5-chlorobenzothiophen-3-yl,5-fluorobenzothiophen-3-yl, 5-bromobenzothiophen-3-yl,5-ethynylbenzothiophen-3-yl, 5-methylbenzothiophen-3-yl,5-chloro-4-fluorobenzothiophen-3-yl, 6-chlorobenzothiophen-3-yl,6-fluorobenzothiophen-3-yl, 6-bromobenzothiophen-3-yl,6-ethynylbenzothiophen-3-yl, 6-methylbenzothiophen-3-yl,5-chlorobenzofuran-2-yl, 5-fluorobenzofuran-2-yl,5-bromobenzofuran-2-yl, 5-ethynylbenzofuran-2-yl,5-methylbenzofuran-2-yl, 5-chloro-4-fluorobenzofuran-2-yl,6-chlorobenzofuran-2-yl, 6-fluorobenzofuran-2-yl,6-bromobenzofuran-2-yl, 6-ethynylbenzofuran-2-yl,6-methylbenzofuran-2-yl, 5-chlorobenzofuran-3-yl,5-fluorobenzofuran-3-yl, 5-bromobenzofuran-3-yl,5-ethynylbenzofuran-3-yl, 5-methylbenzofuran-3-yl,5-chloro-4-fluorobenzofuran-3-yl, 6-chlorobenzofuran-3-yl,6-fluorobenzofuran-3-yl, 6-bromobenzofuran-3-yl,6-ethynylbenzofuran-3-yl, or 6-methylbenzofuran-3-yl.

More preferably, the group is, among others, 5-chloroindol-2-yl,5-fluoroindol-2-yl, 5-bromoindol-2-yl, 5-ethynylindol-2-yl,5-methylindol-2-yl, 5-chloro-4-fluoroindol-2-yl, 6-chloroindol-2-yl,6-fluoroindol-2-yl, 6-bromoindol-2-yl, 6-ethynylindol-2-yl,6-methylindol-2-yl, 5-chloro-3-fluoroindol-2-yl,3-bromo-5-chloroindol-2-yl, 3-chloro-5-fluoroindol-2-yl,5-bromo-5-fluoroindol-2-yl, 5-bromo-3-chloroindol-2-yl,5-bromo-3-fluoroindol-2-yl, 5-chloro-3-formylindol-2-yl,5-fluoro-3-formylindol-2-yl, 5-bromo-3-formylindol-2-yl,5-ethynyl-3-formylindol-2-yl,5-chloro-3-(N,N-dimethylcarbamoyl)indol-2-yl,5-fluoro-3-(N,N-dimethylcarbamoyl)indol-2-yl,5-bromo-3-(N,N-dimethylcarbamoyl)indol-2-yl,5-ethynyl-3-(N,N-dimethylcarbamoyl)indol-2-yl,5-chlorobenzothiophen-2-yl, 5-fluorobenzothiophen-2-yl,5-bromobenzothiophen-2-yl, 5-ethynylbenzothiophen-2-yl,5-methylbenzothiophen-2-yl, 5-chloro-4-fluorobenzothiophen-2-yl,6-chlorobenzothiophen-2-yl, 6-fluorobenzothiophen-2-yl,6-bromobenzothiophen-2-yl, 6-ethynylbenzothiophen-2-yl,6-methylbenzothiophen-2-yl, 5-chlorobenzofuran-2-yl,5-fluorobenzofuran-2-yl, 5-bromobenzofuran-2-yl,5-ethynylbenzofuran-2-yl, 5-methylbenzofuran-2-yl,5-chloro-4-fluorobenzofuran-2-yl, 6-chlorobenzofuran-2-yl,6-fluorobenzofuran-2-yl, 6-bromobenzofuran-2-yl,6-ethynylbenzofuran-2-yl, or 6-methylbenzofuran-2-yl.

In the following group:

(wherein X², X³, X⁴, R¹⁷, and R¹⁸ have the same meanings as describedabove, and numerals “4” to “7” represent positions), X² is preferablyNH, O, or S. The case where any one of X³ and X⁴ is CH or C ispreferred, and the case where one of X³ and X⁴ is C is particularlypreferred. Preferably, R¹⁷ and R¹⁸ each independently represent ahydrogen atom, cyano, a halogen atom, alkyl, alkenyl, alkynyl, orhalogenoalkyl. Preferably, one of R¹⁷ and R¹⁸ is a hydrogen atom, andthe other group is a hydrogen atom, cyano, a halogen atom, alkyl,alkenyl, alkynyl, or halogenoalkyl. Among the cases in which one of R¹⁷and R¹⁸ is a hydrogen atom, the other group is more preferably ahydrogen atom, a halogen atom, alkyl, or alkynyl. In this case, thehalogen atom is preferably a fluorine atom, a chlorine atom, or abromine atom, the alkyl group is preferably a methyl group, and thealkynyl group is preferably ethynyl.

No particular limitation is imposed on the position to which a halogenatom, alkyl, or alkynyl is linked. Among them, 5-position or 6-positionis preferred. Specific examples of preferred groups represented by theabove formula include 5-chloroindazolyl, 5-fluoroindazolyl,5-bromoindazolyl, 5-ethynylindazolyl, 6-chloroindazolyl,6-fluoroindazolyl, 6-bromoindazolyl, 6-ethynylindazolyl,5-chlorobenzimidazolyl, 5-fluorobenzimidazolyl, 5-bromobenzimidazolyl,5-ethynylbenzimidazolyl, 6-chlorobenzimidazolyl, 6-fluorobenzimidazolyl,6-bromobenzimidazolyl, 6-ethynylbenzimidazolyl, 5-chlorobenzothiazolyl,5-fluorobenzothiazolyl, 5-bromobenzothiazolyl, 5-ethynylbenzothiazolyl,6-chlorobenzothiazolyl, 6-fluorobenzothiazolyl, 6-bromobenzothiazolyl,6-ethynylbenzothiazolyl, 5-chlorobenzoxazolyl, 5-fluorobenzoxazolyl,5-bromobenzoxazolyl, 5-ethynylbenzoxazolyl, 6-chlorobenzoxazolyl,6-fluorobenzoxazolyl, 6-bromobenzoxazolyl, 6-ethynylbenzoxazolyl,5-chlorobenzoisothiazolyl, 5-fluorobenzoisothiazolyl,5-bromobenzoisothiazolyl, 5-ethynylbenzoisothiazolyl,6-chlorobenzoisothiazolyl, 6-fluorobenzoisothiazolyl,6-bromobenzoisothiazolyl, 6-ethynylbenzoisothiazolyl,5-chlorobenzoisoxazolyl, 5-fluorobenzoisoxazolyl,5-bromobenzoisoxazolyl, 5-ethynylbenzoisoxazolyl,6-chlorobenzoisoxazolyl, 6-fluorobenzoisoxazolyl,6-bromobenzoisoxazolyl, and 6-ethynylbenzoisoxazolyl.

No particular limitation is imposed on the position, in any of thesesubstituents, to which T¹ is linked. However, the group is preferably5-chloroindazol-3-yl, 5-fluoroindazol-3-yl, 5-bromoindazol-3-yl,5-ethynylindazol-3-yl, 6-chloroindazol-3-yl, 6-fluoroindazol-3-yl,6-bromoindazol-3-yl, 6-ethynylindazol-3-yl, 5-chlorobenzimidazol-2-yl,5-fluorobenzimidazol-2-yl, 5-bromobenzimidazol-2-yl,5-ethynylbenzimidazol-2-yl, 6-chlorobenzimidazol-2-yl,6-fluorobenzimidazol-2-yl, 6-bromobenzimidazol-2-yl,6-ethynylbenzimidazol-2-yl, 5-chlorobenzothiazol-2-yl,5-fluorobenzothiazol-2-yl, 5-bromobenzothiazol-2-yl,5-ethynylbenzothiazol-2-yl, 6-chlorobenzothiazol-2-yl,6-fluorobenzothiazol-2-yl, 6-bromobenzothiazol-2-yl,6-ethynylbenzothiazol-2-yl, 5-chlorobenzoxazol-2-yl,5-fluorobenzoxazol-2-yl, 5-bromobenzoxazol-2-yl,5-ethynylbenzoxazol-2-yl, 6-chlorobenzoxazol-2-yl,6-fluorobenzoxazol-2-yl, 6-bromobenzoxazol-2-yl,6-ethynylbenzoxazol-2-yl, 5-chlorobenzoisothiazol-3-yl,5-fluorobenzoisothiazol-3-yl, 5-bromobenzoisothiazol-3-yl,5-ethynylbenzoisothiazol-3-yl, 6-chlorobenzoisothiazol-3-yl,6-fluorobenzoisothiazol-3-yl, 6-bromobenzoisothiazol-3-yl,6-ethynylbenzoisothiazol-3-yl, 5-chlorobenzoisoxazol-3-yl,5-fluorobenzoisoxazol-3-yl, 5-bromobenzoisoxazol-3-yl,5-ethynylbenzoisoxazol-3-yl, 6-chlorobenzoisoxazol-3-yl,6-fluorobenzoisoxazol-3-yl, 6-bromobenzoisoxazol-3-yl, or6-ethynylbenzoisoxazol-3-yl.

The group is more preferably 5-chlorobenzimidazol-2-yl,5-fluorobenzimidazol-2-yl, 5-bromobenzimidazol-2-yl,5-ethynylbenzimidazol-2-yl, 6-chlorobenzimidazol-2-yl,6-fluorobenzimidazol-2-yl, 6-bromobenzimidazol-2-yl,6-ethynylbenzimidazol-2-yl, 5-chlorobenzothiazol-2-yl,5-fluorobenzothiazol-2-yl, 5-bromobenzothiazol-2-yl,5-ethynylbenzothiazol-2-yl, 6-chlorobenzothiazol-2-yl,6-fluorobenzothiazol-2-yl, 6-bromobenzothiazol-2-yl,6-ethynylbenzothiazol-2-yl, 5-chlorobenzoxazol-2-yl,5-fluorobenzoxazol-2-yl, 5-bromobenzoxazol-2-yl,5-ethynylbenzoxazol-2-yl, 6-chlorobenzoxazol-2-yl,6-fluorobenzoxazol-2-yl, 6-bromobenzoxazol-2-yl, and6-ethynylbenzoxazol-2-yl, still more preferably5-chlorobenzimidazol-2-yl, 5-fluorobenzimidazol-2-yl,5-bromobenzimidazol-2-yl, or 5-ethynylbenzimidazol-2-yl.

In the following group:

(wherein N denotes that one or two ring carbon atoms of the ring havingR¹⁹ and being represented with reference “N” are substituted bynitrogen, R¹⁹, R²⁰, and R²¹ have the same meanings as described above,and numerals “5” to “8” represent positions) each of R¹⁹, R²⁰, and R²¹represents a hydrogen atom, cyano, a halogen atom, alkyl, alkenyl,alkynyl, or halogenoalkyl. R¹⁹ is particularly preferably a hydrogenatom. Preferably, one of R²⁰ and R²¹ is a hydrogen atom, and the othergroup is a hydrogen atom, cyano, a halogen atom, alkyl, alkenyl,alkynyl, or halogenoalkyl. Among the cases in which one of R²⁰ and R²¹is a hydrogen atom, the other group is more preferably a hydrogen atom,a halogen atom, alkyl, or alkynyl. In this case, the halogen atom ispreferably a fluorine atom, a chlorine atom, or a bromine atom, thealkyl group is preferably a methyl group, and the alkynyl group ispreferably an ethynyl group. No particular limitation is imposed on theposition to which a halogen atom, alkyl, or alkynyl is linked. Amongthem, 6-position or 7-position is preferred.

Specific examples of the group represented by the above formula includequinolinyl, isoquinolinyl, and cinnolinyl. Among them, the group ispreferably, among others, 6-chloroquinolinyl, 6-fluoroquinolinyl,6-bromoquinolinyl, 6-ethynylquinolinyl, 6-chloroisoquinolinyl,6-fluoroisoquinolinyl, 6-bromoisoquinolinyl, 6-ethynylisoquinolinyl,7-chlorocinnolinyl, 7-fluorocinnolinyl, 7-bromocinnolinyl, or7-ethynylcinnolinyl, more preferably, among others,6-chloroquinolin-2-yl, 6-fluoroquinolin-2-yl, 6-bromoquinolin-2-yl,6-ethynylquinolin-2-yl, 6-chloroquinolin-3-yl, 6-fluoroquinolin-3-yl,6-bromoquinolin-3-yl, 6-ethynylquinolin-3-yl, 7-chloroquinolin-2-yl,7-fluoroquinolin-2-yl, 7-bromoquinolin-2-yl, 7-ethynylquinolin-2-yl,7-chloroquinolin-3-yl, 7-fluoroquinolin-3-yl, 7-bromoquinolin-3-yl,7-ethynylquinolin-3-yl, 6-chloroisoquinolin-3-yl,6-fluoroisoquinolin-3-yl, 6-bromoisoquinolin-3-yl,6-ethynylisoquinolin-3-yl, 7-chloroisoquinolin-3-yl,7-fluoroisoquinolin-3-yl, 7-bromoisoquinolin-3-yl,7-ethynylisoquinolin-3-yl, 7-chlorocinnolin-3-yl, 7-fluorocinnolin-3-yl,7-bromocinnolin-3-yl, or 7-ethynylcinnolin-3-yl.

Among them, the group is still more preferably 6-chloroquinolin-2-yl,6-fluoroquinolin-2-yl, 6-bromoquinolin-2-yl, 6-ethynylquinolin-2-yl,7-chloroquinolin-3-yl, 7-fluoroquinolin-3-yl, 7-bromoquinolin-3-yl,7-ethynylquinolin-3-yl, 7-chloroisoquinolin-3-yl,7-fluoroisoquinolin-3-yl, 7-bromoisoquinolin-3-yl,7-ethynylisoquinolin-3-yl, 7-chlorocinnolin-3-yl, 7-fluorocinnolin-3-yl,7-bromocinnolin-3-yl, or 7-ethynylcinnolin-3-yl.

In the following group:

(wherein numerals “5” to “8” represent positions; X⁵ represents CH₂, CH,N, or NH; Z¹ represents N, NH, or O; Z² represents CH₂, CH, C, or N; Z³represents CH₂, CH, S, SO₂, or C═O; X⁵—Z² represents a moiety in whichX⁵ and Z² are linked via a single bond or a double bond; R²², R²³, andR²⁴ have the same meanings as described above) each of R²² and R²³ ispreferably a hydrogen atom, cyano, a halogen atom, alkyl, alkenyl,alkynyl, or halogenoalkyl. Preferably, one of R²² and R²³ is a hydrogenatom, and the other group is a hydrogen atom, cyano, a halogen atom,alkyl, alkenyl, alkynyl, or halogenoalkyl. Among the cases in which oneof R²² and R²³ is a hydrogen atom, the other group is more preferably ahydrogen atom, a halogen atom, alkyl, or alkynyl. In this case, thehalogen atom is preferably a fluorine atom, a chlorine atom, and abromine atom, the alkyl group is preferably a methyl group, and thealkynyl group is preferably an ethynyl group. No particular limitationis imposed on the position to which a halogen atom, alkyl, or alkynyl islinked. Among them, 6-position or 7-position is preferred. R²⁴ ispreferably a hydrogen atom or alkyl. Among alkyl groups, methyl ispreferred. R²⁴ is particularly preferably a hydrogen atom.

Specific examples of groups represented by the above formula include4-oxodihydroquinolinyl, tetrahydroquinolinyl,4-oxodihydroquinazolin-2-yl, 4-oxotetrahydroicinnolinyl,4-oxobenzopyranyl, 4-oxobenzothiadiazinyl,1,1-dioxy-4-oxobenzothiadiazinyl, and benzoxadiazinyl.

More specific examples of the group include6-chloro-4-oxodihydroquinolinyl, 6-fluoro-4-oxodihydroquinolinyl,6-bromo-4-oxodihydroquinolinyl, 6-ethynyl-4-oxodihydroquinolinyl,7-chloro-4-oxodihydroquinolinyl, 7-fluoro-4-oxodihydroquinolinyl,7-bromo-4-oxodihydroquinolinyl, 7-ethynyl-4-oxodihydroquinolinyl,6-chloro-4-oxo-1,4-dihydroquinazolinyl,6-fluoro-4-oxo-1,4-dihydroquinazolinyl,6-bromo-4-oxo-1,4-dihydroquinazolinyl,6-ethynyl-4-oxo-1,4-dihydroquinazolinyl,7-chloro-4-oxo-1,4-dihydroquinazolinyl,7-fluoro-4-oxo-1,4-dihydroquinazolinyl,7-bromo-4-oxo-1,4-dihydroquinazolinyl,7-ethynyl-4-oxo-1,4-dihydroquinazolinyl,6-chloro-1,2,3,4-tetrahydroquinolinyl,6-fluoro-1,2,3,4-tetrahydroquinolinyl,6-bromo-1,2,3,4-tetrahydroquinolinyl,6-ethynyl-1,2,3,4-tetrahydroquinolinyl,7-chloro-1,2,3,4-tetrahydroquinolinyl,7-fluoro-1,2,3,4-tetrahydroquinolinyl,7-bromo-1,2,3,4-tetrahydroquinolinyl,7-ethynyl-1,2,3,4-tetrahydroquinolinyl,6-chloro-1,2,3,4-tetrahydro-4-oxocinnolinyl,6-fluoro-1,2,3,4-tetrahydro-4-oxocinnolinyl,6-bromo-1,2,3,4-tetrahydro-4-oxocinnolinyl,6-ethynyl-1,2,3,4-tetrahydro-4-oxocinnolinyl,7-chloro-1,2,3,4-tetrahydro-4-oxocinnolinyl,7-fluoro-1,2,3,4-tetrahydro-4-oxocinnolinyl,7-bromo-1,2,3,4-tetrahydro-4-oxocinnolinyl,7-ethynyl-1,2,3,4-tetrahydro-4-oxocinnolinyl,6-chloro-4H-4-oxobenzopyranyl, 6-fluoro-4H-4-oxobenzopyranyl,6-bromo-4H-4-oxobenzopyranyl, 6-ethynyl-4H-4-oxobenzopyranyl,7-chloro-4H-4-oxobenzopyranyl, 7-fluoro-4H-4-oxobenzopyranyl,7-bromo-4H-4-oxobenzopyranyl, 7-ethynyl-4H-4-oxobenzopyranyl,6-chloro-1,1-dioxy-2H-1,2,4-benzothiadiazinyl,6-fluoro-1,1-dioxy-2H-1,2,4-benzothiadiazinyl,6-bromo-1,1-dioxy-2H-1,2,4-benzothiadiazinyl,6-ethynyl-1,1-dioxy-2H-1,2,4-benzothiadiazinyl,7-chloro-1,1-dioxy-2H-1,2,4-benzothiadiazinyl,7-fluoro-1,1-dioxy-2H-1,2,4-benzothiadiazinyl,7-bromo-1,1-dioxy-2H-1,2,4-benzothiadiazinyl,7-ethynyl-1,1-dioxy-2H-1,2,4-benzothiadiazinyl,6-chloro-2H-1,2,4-benzoxadiazinyl, 6-fluoro-2H-1,2,4-benzoxadiazinyl,6-bromo-2H-1,2,4-benzoxadiazinyl, 6-ethynyl-2H-1,2,4-benzoxadiazinyl,7-chloro-2H-1,2,4-benzoxadiazinyl, 7-fluoro-2H-1,2,4-benzoxadiazinyl,7-bromo-2H-1,2,4-benzoxadiazinyl, and7-ethynyl-2H-1,2,4-benzoxadiazinyl.

Particularly preferred are, for example,6-chloro-4-oxo-1,4-dihydroquinolin-2-yl,6-fluoro-4-oxo-1,4-dihydroquinolin-2-yl,6-bromo-4-oxo-1,4-dihydroquinolin-2-yl,6-ethynyl-4-oxo-1,4-dihydroquinolin-2-yl,7-chloro-4-oxo-1,4-dihydroquinolin-2-yl,7-fluoro-4-oxo-1,4-dihydroquinolin-2-yl,7-bromo-4-oxo-1,4-dihydroquinolin-2-yl,7-ethynyl-4-oxo-1,4-dihydroquinolin-2-yl,6-chloro-4-oxo-1,4-dihydroquinazolin-2-yl,6-fluoro-4-oxo-1,4-dihydroquinazolin-2-yl,6-bromo-4-oxo-1,4-dihydroquinazolin-2-yl,6-ethynyl-4-oxo-1,4-dihydroquinazolin-2-yl,7-chloro-4-oxo-1,4-dihydroquinazolin-2-yl,7-fluoro-4-oxo-1,4-dihydroquinazolin-2-yl,7-bromo-4-oxo-1,4-dihydroquinazolin-2-yl,7-ethynyl-4-oxo-1,4-dihydroquinazolin-2-yl,6-chloro-1,2,3,4-tetrahydroquinolin-2-yl,6-fluoro-1,2,3,4-tetrahydroquinolin-2-yl,6-bromo-1,2,3,4-tetrahydroquinolin-2-yl,6-ethynyl-1,2,3,4-tetrahydroquinolin-2-yl,6-chloro-1,2,3,4-tetrahydro-4-oxocinnolin-2-yl,6-fluoro-1,2,3,4-tetrahydro-4-oxocinnolin-2-yl,6-bromo-1,2,3,4-tetrahydro-4-oxocinnolin-2-yl,6-ethynyl-1,2,3,4-tetrahydro-4-oxocinnolin-2-yl,7-chloro-1,2,3,4-tetrahydro-4-oxocinnolin-2-yl,7-fluoro-1,2,3,4-tetrahydro-4-oxocinnolin-2-yl,7-bromo-1,2,3,4-tetrahydro-4-oxocinnolin-2-yl,7-ethynyl-1,2,3,4-tetrahydro-4-oxocinnolin-2-yl,6-chloro-4H-4-oxobenzopyran-2-yl, 6-fluoro-4H-4-oxobenzopyran-2-yl,6-bromo-4H-4-oxobenzopyran-2-yl, 6-ethynyl-4H-4-oxobenzopyran-2-yl,7-chloro-4H-4-oxobenzopyran-2-yl, 7-fluoro-4H-4-oxobenzopyran-2-yl,7-bromo-4H-4-oxobenzopyran-2-yl, 7-ethynyl-4H-4-oxobenzopyran-2-yl,6-chloro-1,1-dioxy-2H-1,2,4-benzothiadiazin-3-yl,6-fluoro-1,1-dioxy-2H-1,2,4-benzothiadiazin-3-yl,6-bromo-1,1-dioxy-2H-1,2,4-benzothiadiazin-3-yl,6-ethynyl-1,1-dioxy-2H-1,2,4-benzothiadiazin-3-yl,7-chloro-1,1-dioxy-2H-1,2,4-benzothiadiazin-3-yl,7-fluoro-1,1-dioxy-2H-1,2,4-benzothiadiazin-3-yl,7-bromo-1,1-dioxy-2H-1,2,4-benzothiadiazin-3-yl,7-ethynyl-1,1-dioxy-2H-1,2,4-benzothiadiazin-3-yl,6-chloro-2H-1,2,4-benzoxadiazin-3-yl,6-fluoro-2H-1,2,4-benzoxadiazin-3-yl,6-bromo-2H-1,2,4-benzoxadiazin-3-yl,6-ethynyl-2H-1,2,4-benzoxadiazin-3-yl,7-chloro-2H-1,2,4-benzoxadiazin-3-yl,7-fluoro-2H-1,2,4-benzoxadiazin-3-yl,7-bromo-2H-1,2,4-benzoxadiazin-3-yl, and7-ethynyl-2H-1,2,4-benzoxadiazin-3-yl.

Among them, still more preferred are6-chloro-4-oxo-1,4-dihydroquinolin-2-yl,6-fluoro-4-oxo-1,4-dihydroquinolin-2-yl,6-bromo-4-oxo-1,4-dihydroquinolin-2-yl,6-ethynyl-4-oxo-1,4-dihydroquinolin-2-yl,6-chloro-4-oxo-1,4-dihydroquinazolin-2-yl,6-fluoro-4-oxo-1,4-dihydroquinazolin-2-yl,6-bromo-4-oxo-1,4-dihydroquinazolin-2-yl, and6-ethynyl-4-oxo-1,4-dihydroquinazolin-2-yl.

In the following group:

(wherein X⁶ represents O or S; R²⁵ and R²⁶ have the same meanings asdescribed above; and numerals “5” to “8” represent positions), X⁶ ispreferably O, and each of R²⁵ and R²⁶ is preferably a hydrogen atom,cyano, a halogen atom, alkyl, alkenyl, alkynyl, or halogenoalkyl.Preferably, one of R²⁵ and R²⁶ is a hydrogen atom, and the other groupis a hydrogen atom, cyano, a halogen atom, alkyl, alkenyl, alkynyl, orhalogenoalkyl. Among the cases in which one of R²⁵ and R²⁶ is a hydrogenatom, the other group is particularly preferably a hydrogen atom, ahalogen atom, alkyl, or alkynyl. In this case, the halogen atom ispreferably a fluorine atom, a chlorine atom, or a bromine atom, thealkyl group is preferably a methyl group, and the alkynyl group is anethynyl group. No particularly limitation is imposed on the position towhich a halogen atom, alkyl, or alkynyl is linked. Among them,6-position or 7-position is preferred.

Specific examples of preferred groups include 6-chloro-2H-chromen-3-yl,6-fluoro-2H-chromen-3-yl, 6-bromo-2H-chromen-3-yl,6-ethynyl-2H-chromen-3-yl, 7-chloro-2 H-chromen-3-yl,7-fluoro-2H-chromen-3-yl, 7-bromo-2H-chromen-3-yl, and7-ethynyl-2H-chromen-3-yl. 7-chloro-2H-chromen-3-yl,7-fluoro-2H-chromen-3-yl, 7-bromo-2H-chromen-3-yl, and7-ethynyl-2H-chromen-3-yl are particularly preferred.

In the following group:

(wherein R²⁷ and R²⁸ have the same meanings as described above, andnumerals “1” to “6” represent positions), preferably, one of R²⁷ and R²⁸is a hydrogen atom or a halogen atom, and the other group is a hydrogenatom, cyano, nitro, amino, a halogen atom, alkyl, alkenyl, alkynyl,halogenoalkyl, or N,N-dialkylcarbamoyl. Among the cases in which one ofR²⁷ and R²⁸ is a hydrogen atom or a halogen atom, the other group isparticularly preferably a hydrogen atom, a halogen atom, alkyl, oralkynyl. In this case, the halogen atom is preferably a fluorine atom, achlorine atom, or a bromine atom, the alkyl group is preferably a methylgroup, and the alkynyl group is particularly preferably an ethynylgroup. Preferred examples of the group represented by the above formulainclude phenyl, chlorophenyl, fluorophenyl, bromophenyl, ethynylphenyl,and chlorofluorophenyl. No particular limitation is imposed on theposition, in any of these groups, to which halogen atom(s), alkyl, oralkynyl is linked. However, when these groups are mono-substituted,3-position and 4-position of the ring in the above formula areparticularly preferred, whereas when these groups are di-substituted,combinations of 4- and 2-positions and 4- and 3-positions of the ring inthe above formula are particularly preferred.

Preferred examples of the group include phenyl, 4-chlorophenyl,4-fluorophenyl, 4-bromophenyl, 4-ethynylphenyl, 3-chlorophenyl,3-fluorophenyl, 3-bromophenyl, 3-ethynylphenyl, 3-chloro-4-fluorophenyl,4-chloro-3-fluorophenyl, 4-chloro-2-fluorophenyl,2-chloro-4-fluorophenyl, 4-bromo-2-fluorophenyl, 2-bromo-4-fluorophenyl,2,4-dichlorophenyl, 2,4-difluorophenyl, 2,4-dibromophenyl,4-chloro-3-methylphenyl, 4-fluoro-3-methylphenyl,4-bromo-3-methylphenyl, 4-chloro-2-methylphenyl,4-fluoro-2-methylphenyl, 4-bromo-2-methylphenyl, 3,4-dichlorophenyl,3,4-difluorophenyl, and 3,4-dibromophenyl.

In the following formula:

(wherein E¹, E², R²⁹, and R³⁰ have the same meanings as described above,and numerals “1” to “6” represent positions), preferably, one of R²⁹ andR³⁰ is a hydrogen atom or a halogen atom, and the other of the group isa hydrogen atom, cyano, a halogen atom, alkyl, alkenyl, alkynyl, orhalogenoalkyl. Among the cases in which one of R²⁹ and R³⁰ is a hydrogenatom or a halogen atom, the other group is particularly preferably ahydrogen atom, a halogen atom, alkyl, or alkynyl. In this case, thehalogen atom is preferably a fluorine atom, a chlorine atom, or abromine atom, the alkyl group is preferably a methyl group, and thealkynyl group is particularly preferably an ethynyl group.

Specific examples of the group represented by the above formula includepyridyl, pyrimidyl, and pyridazinyl. No particular limitation is imposedon the position, in any of these groups, to which a halogen atom, alkyl,or alkynyl is linked. However, when T¹ is linked to the group on the2-position of the ring in the above formula, 4-position and 5-positionof the ring in the above formula are particularly preferred.

Specifically, preferred examples of the group include 2-pyridyl,3-pyridyl, 4-pyridyl, 4-chloro-2-pyridyl, 4-fluoro-2-pyridyl,4-bromo-2-pyridyl, 4-ethynyl-2-pyridyl, 4-chloro-3-pyridyl,4-fluoro-3-pyridyl, 4-bromo-3-pyridyl, 4-ethynyl-3-pyridyl,5-chloro-2-pyridyl, 5-fluoro-2-pyridyl, 5-bromo-2-pyridyl,5-ethynyl-2-pyridyl, 4-chloro-5-fluoro-2-pyridyl,5-chloro-4-fluoro-2-pyridyl, 5-chloro-3-pyridyl, 5-fluoro-3-pyridyl,5-bromo-3-pyridyl, 5-ethynyl-3-pyridyl, 5-chloro-2-pyrimidyl,5-fluoro-2-pyrimidyl, 5-bromo-2-pyrimidyl, 5-ethynyl-2-pyrimidyl,4-chloro-3-pyridazinyl, 4-fluoro-3-pyridazinyl, 4-bromo-3-pyridazinyl,4-ethynyl-3-pyridazinyl, 6-chloro-3-pyridazinyl, 6-fluoro-3-pyridazinyl,6-bromo-3-pyridazinyl, and 6-ethynyl-3-pyridazinyl.

Among them, particularly preferred are 2-pyridyl, 3-pyridyl, 4-pyridyl,4-chloro-2-pyridyl, 4-fluoro-2-pyridyl, 4-bromo-2-pyridyl,4-ethynyl-2-pyridyl, 4-chloro-3-pyridyl, 4-fluoro-2-fluoro-3-pyridyl,4-bromo-3-pyridyl, 4-ethynyl-3-pyridyl, 5-chloro-2-pyridyl,5-fluoro-2-pyridyl, 5-bromo-2-pyridyl, 5-ethynyl-2-pyridyl,4-chloro-5-fluoro-2-pyridyl, 5-chloro-4-fluoro-2-pyridyl,5-chloro-3-pyridyl, 5-fluoro-3-pyridyl, 5-bromo-3-pyridyl,5-ethynyl-3-pyridyl, 6-chloro-3-pyridazinyl, 6-fluoro-3-pyridazinyl,6-bromo-3-pyridazinyl, 6-ethynyl-3-pyridazinyl, 4-chloro-3-pyridazinyl,4-fluoro-3-pyridazinyl, 4-bromo-3-pyridazinyl, and4-ethynyl-3-pyridazinyl.

Among them, still more preferred are 2-pyridyl, 3-pyridyl, 4-pyridyl,5-chloro-2-pyridyl, 5-fluoro-2-pyridyl, 5-bromo-2-pyridyl,5-ethynyl-2-pyridyl, 5-chloro-4-fluoro-2-pyridyl,4-chloro-5-fluoro-2-pyridyl, 4-chloro-3-pyridazinyl,4-fluoro-3-pyridazinyl, 4-bromo-3-pyridazinyl, and4-ethynyl-3-pyridazinyl.

In the following group:

(wherein Y¹, Y², R³¹ and R³² have the same meanings as described above,and numerals “1” to “5” represent positions), preferably, one of R³¹ andR³² is a hydrogen atom or a halogen atom, and the other group is ahydrogen atom, cyano, a halogen atom, alkyl, alkenyl, alkynyl, orhalogenoalkyl. Among the cases in which one of R³¹ and R³² is a hydrogenatom or a halogen atom, the other group is particularly preferably ahydrogen atom, a halogen atom, alkyl, or alkynyl. In these cases, thehalogen atom is preferably a fluorine atom, a chlorine atom, or abromine atom, the alkyl group is preferably methyl, and the alkynylgroup is particularly preferred ethynyl.

Specific examples of the group represented by the above formula includethienyl, pyrrolyl, furyl, oxazolyl, and thiazolyl. No particularlimitation is imposed on the position, in any of these groups, to whicha halogen atom, alkyl, or alkynyl is linked. Among them, 4-position and5-position are particularly preferred.

Specific examples of the group include 4-chloro-2-thienyl,4-fluoro-2-thienyl, 4-bromo-2-thienyl, 4-ethynyl-2-thienyl,4-chloro-2-pyrrolyl, 4-fluoro-2-pyrrolyl, 4-bromo-2-pyrrolyl,4-ethynyl-2-pyrrolyl, 4-chloro-2-furyl, 4-fluoro-2-furyl,4-bromo-2-furyl, 4-ethynyl-2-furyl, 5-chloro-2-thienyl,5-fluoro-2-thienyl, 5-bromo-2-thienyl, 5-ethynyl-2-thienyl,5-chloro-2-thiazolyl, 5-fluoro-2-thiazolyl, 5-bromo-2-thiazolyl,5-ethynyl-2-thiazolyl, 5-chloro-2-oxazolyl, 5-fluoro-2-oxazolyl,5-bromo-2-oxazolyl, and 5-ethynyl-2-oxazolyl. Among them,5-chloro-2-thiazolyl, 5-fluoro-2-thiazolyl, 5-bromo-2-thiazolyl, and5-ethynyl-2-thiazolyl are preferred.

Furthermore, in the following group:

(wherein, numerals “1” to “8” represent positions, each N indicates thatany one of carbon atoms of positions 1 to 4 and any one of carbon atomsof positions 5 to 8 has been substituted by a nitrogen atom, and R³⁴ toR³⁶ have the same meanings as described above), the substituent nitrogenatoms may locate at any positions, R³⁴ is preferably a hydrogen atom ora halogen atom. One of R³⁵ and R³⁶ is a hydrogen atom or a halogen atom,and the other group is a hydrogen atom, cyano, halogen atom, alkyl,alkenyl, alkynyl or halogenoalkyl. Among the cases in which one of R³⁵and R³⁶ is a hydrogen atom or a halogen atom, the other group isparticularly preferably a hydrogen atom, a halogen atom, alkyl oralkynyl. The halogen atom is preferably a fluorine atom, a chlorineatom, or a bromine atom, the alkyl group is a methyl group, and thealkynyl group is particularly preferably an ethynyl group.

No particular limitation is imposed on the position to which a halogenatom, alkyl, or alkynyl is linked. Specific examples of the grouprepresented by the above formula include 6-chloro-1,5-naphthyridin-2-yl,6-fluoro-1,5-naphthyridin-2-yl, 6-bromo-1,5-naphthyridin-2-yl,6-ethynyl-1,5-naphthyridin-2-yl, 7-chloro-1,5-naphthyridin-2-yl,7-fluoro-1,5-naphthyridin-2-yl, 7-bromo-1,5-naphthyridin-2-yl,7-ethynyl-1,5-naphthyridin-2-yl, 6-chloro-1,5-naphthyridin-3-yl,6-fluoro-1,5-naphthyridin-3-yl, 6-bromo-1,5-naphthyridin-3-yl,6-ethynyl-1,5-naphthyridin-3-yl, 7-chloro-1,5-naphthyridin-3-yl,7-fluoro-1,5-naphthyridin-3-yl, 7-bromo-1,5-naphthyridin-3-yl,7-ethynyl-1,5-naphthyridin-3-yl, 6-chloro-1,7-naphthyridin-2-yl,6-fluoro-1,7-naphthyridin-2-yl, 6-bromo-1,7-naphthyridin-2-yl,6-ethynyl-1,7-naphthyridin-2-yl, 6-chloro-1,7-naphthyridin-3-yl,6-fluoro-1,7-naphthyridin-3-yl, 6-bromo-1,7-naphthyridin-3-yl,6-ethynyl-1,7-naphthyridin-3-yl, 6-chloro-1,8-naphthyridin-2-yl,6-fluoro-1,8-naphthyridin-2-yl, 6-bromo-1,8-naphthyridin-2-yl,6-ethynyl-1,8-naphthyridin-2-yl, 7-chloro-1,8-naphthyridin-2-yl,7-fluoro-1,8-naphthyridin-2-yl, 7-bromo-1,8-naphthyridin-2-yl,7-ethynyl-1,8-naphthyridin-2-yl, 6-chloro-1,8-naphthyridin-3-yl,6-fluoro-1,8-naphthyridin-3-yl, 6-bromo-1,8-naphthyridin-3-yl,6-ethynyl-1,8-naphthyridin-3-yl, 7-chloro-1,8-naphthyridin-3-yl,7-fluoro-1,8-naphthyridin-3-yl, 7-bromo-1,8-naphthyridin-3-yl,7-ethynyl-1,8-naphthyridin-3-yl, 6-chloro-2,5-naphthyridin-3-yl,6-fluoro-2,5-naphthyridin-3-yl, 6-bromo-2,5-naphthyridin-3-yl,6-ethynyl-2,5-naphthyridin-3-yl, 7-chloro-2,5-naphthyridin-3-yl,7-fluoro-2,5-naphthyridin-3-yl, 7-bromo-2,5-naphthyridin-3-yl,7-ethynyl-2,5-naphthyridin-3-yl, 7-chloro-2,6-naphthyridin-3-yl,7-fluoro-2,6-naphthyridin-3-yl, 7-bromo-2,6-naphthyridin-3-yl,7-ethynyl-2,6-naphthyridin-3-yl, 6-chloro-2,8-naphthyridin-3-yl,6-fluoro-2,8-naphthyridin-3-yl, 6-bromo-2,8-naphthyridin-3-yl,6-ethynyl-2,8-naphthyridin-3-yl, 7-chloro-2,8-naphthyridin-3-yl,7-fluoro-2,8-naphthyridin-3-yl, 7-bromo-2,8-naphthyridin-3-yl, and7-ethynyl-2,8-naphthyridin-3-yl.

Particularly preferred examples of the group include7-chloro-2,5-naphthyridin-3-yl, 7-fluoro-2,5-naphthyridin-3-yl,7-bromo-2,5-naphthyridin-3-yl, and 7-ethynyl-2,5-naphthyridin-3-yl.

In addition to the above 12 groups (a) to (l), a thienopyrrolyl groupwhich may be substituted is also preferred. The thienopyrrolyl group mayhave 1 to 3 substituents, and examples of the substituent(s) includehydroxyl, nitro, amino, cyano, a halogen atom, alkyl, alkenyl, alkynyl,halogenoalkyl, hydroxyalkyl, alkoxy, alkoxyalkyl, carboxyl,carboxyalkyl, acyl, carbamoyl, N-alkylcarbamoyl, N,N-dialkylcarbamoyl,alkoxycarbonyl, amidino, and alkoxycarbonylalkyl. Among them, cyano, ahalogen atom, alkyl, alkenyl, alkynyl, and halogenoalkyl are preferred.

Specifically, preferred examples include2-chlorothieno[2,3-b]pyrrol-5-yl, 2-fluorothieno[2,3-b]pyrrol-5-yl,2-bromothieno[2,3-b]pyrrol-5-yl, and 2-ethynylthieno[2,3-b]pyrrol-5-yl.

Next will be described, in detail, the following group:

[wherein Q¹, R³, and R⁴ have the same meanings as described above, and 1and 2 denotes positions].

The moiety having a cyclic structure containing the above group Q¹ is a3- to 10-membered divalent cyclic hydrocarbon group which may have onedouble bond, or a 5- to 12-membered divalent heterocyclic group whichhas 2 heteroatoms. The moiety is preferably a 3- to 8-membered divalentcyclic hydrocarbon group or a 5- to 8-membered divalent heterocyclicgroup, more preferably a 5- to 7-membered divalent cyclic hydrocarbongroup or a 5- to 7-membered divalent heterocyclic group. Of these,preferred is a group in which Q¹ represents a C3-C6 alkylene group or agroup (CH₂)_(m)—CH₂-A-CH₂—(CH₂)_(n)— (wherein each of m and n isindependently 0 or 1, and A has the same meaning as described above).Particularly preferred is a group in which Q¹ represents a C4 alkylenegroup.

The cyclic hydrocarbon or heterocyclic group may have cis-formation ortrans-formation with respect to the 1-position and the 2-position. Inthe case of 5-membered ring, trans-formation is preferred. In the caseof 6- or 7-membered ring, cis- and trans-formations are both preferred.

The above substituents R³ and R⁴ will next be described in detail. Thehalogen atom is a fluorine atom, chlorine atom, bromine atom, or iodineatom. Examples of the alkyl group include a linear, branched, or cyclicC₁-C₆ alkyl (e.g., methyl, cyclopropyl, isobutyl), examples of thehalogenoalkyl group include a group corresponding to the above alkylgroup which has been substituted by 1 to 3 halogen atoms (e.g.,chloromethyl, 1-bromoethyl, trifluoromethyl). Examples of the cyanoalkylgroup include a group corresponding to the above C₁-C₆ alkyl group whichhas been substituted by a single cyano group (e.g., cyanomethyl,1-cyanoethyl). Examples of the alkenyl group include a linear orbranched C2-C6 alkenyl group having a single double bond (e.g., vinyl,allyl). Examples of the alkynyl group include a linear or branched C2-C6alkynyl group having a single triple bond (e.g., ethynyl, propynyl).Examples of the acyl group include a C₁-C₆ alkanoyl group (e.g., formyl,acetyl), a C₇-C₁₅ aroyl group (e.g., benzoyl, naphthoyl), and anarylalkanoyl group corresponding to the above C₁-C₆ alkanoyl group whichhas been substituted by one of the C₆-C₁₄ aryl groups mentioned above(e.g., phenacetyl). Examples of the acylalkyl group include a groupcorresponding to the above C₁-C₆ alkyl group which has been substitutedby one of the acyl groups mentioned above (e.g., acetylmethyl). Examplesof the alkoxy group include a linear, branched, or cyclic C₁-C₆ alkoxygroup (e.g., methoxy, cyclopropoxy, isopropoxy). Examples of thealkoxyalkyl groups include a group corresponding to the above C₁-C₆alkyl group which has been substituted by one of the C₁-C₆ alkoxy groupsmentioned above (e.g., methoxymethyl, ethoxymethyl). Examples of thehydroxyalkyl groups include a group corresponding to the above C₁-C₆alkyl group which has been substituted by a single hydroxyl group (e.g.,hydroxymethyl, 1-hydroxyethyl). Examples of the carboxyalkyl groupsinclude a group corresponding to the above C₁-C₆ alkyl group which hasbeen substituted by a single carboxyl group (e.g., carboxymethyl,1-carboxyethyl). Examples of the alkoxycarbonyl group include a groupformed of the above C₁-C₆ alkoxy groups and a carbonyl group (e.g.,methoxycarbonyl, ethoxycarbonyl). Examples of the alkoxycarbonylalkylgroup include a group corresponding to the above C₁-C₆ alkyl group whichhas been substituted by one of the alkoxycarbonyl groups mentioned above(e.g., methoxycarbonylethyl, ethoxycarbonylethyl). Examples of thecarbamoylalkyl group include a group corresponding to the above C₁-C₆alkyl group which has been substituted by a carbamoyl group (e.g.,carbamoylmethyl, carbamoylethyl).

The 3- to 6-membered heterocyclic group which may have a substituent isa saturated or unsaturated 3- to 6-membered heterocyclic group which mayhave 1 to 3 heteroatoms (e.g., nitrogen atom, oxygen atom, sulfur atom),and the heterocyclic group may have a substituent such as hydroxy, ahalogen atom, amino, C₁-C₆ alkyl, oxo, or halogenoalkyl. Examples of the3- to 6-membered heterocyclic group include pyrrolyl, thienyl,pyrazolyl, imidazolyl, pyrazolinyl, oxazolyl, oxazolinyl, oxadiazolyl,oxazolidinyl, thiazolyl, thiazolinyl, thiadiazolyl, furazanyl, pyranyl,pyridyl, pyrimidyl, pyridazinyl, pyrrolidinyl, piperazinyl, piperidinyl,oxazinyl, oxadiazinyl, morpholinyl, thiazinyl, thiadiazinyl,thiomorpholinyl, tetrazolyl, triazolyl, and triazinyl.

Specific examples of the 3- to 6-membered heterocyclic group which mayhave a substituent include thiazolyl, 4,5-dihydrothiazolyl, oxazolyl,4,5-dihydroxazolyl, 5-methyloxazolyl, imidazolyl, pyrrolidinyl,3-hydroxypyrrolidinyl, piperidyl, piperazinyl, morpholinyl,thiomorpholinyl, 1,1-dioxothiomorpholinyl, tetrahydropyranyl, pyridyl,1,2,4-oxadiazolyl, 3-methyl-1,2,4-oxadiazolyl,5-methyl-1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl,5-methyl-1,3,4-oxadiazolyl, 5-(trifluoromethyl)-1,3,4-oxadiazolyl,1,3-oxazolyl, 1,3,4-thiadiazolyl, 5-methyl-1,3,4-thiadiazolyl, and1,3-oxazolidinyl.

Examples of the 3- to 6-membered heterocyclic alkyl group which may havea substituent include a group corresponding to the above 3- to6-membered heterocyclic group which may have a substituent, which grouphas been substituted by a single alkyl group (e.g., thiazolylmethyl,4,5-dihydrothiazolylmethyl, morpholinylmethyl,1,1-dioxothiomorpholinylmethyl). Examples of the aryl group includeC6-C14 aryl groups such as phenyl and naphthyl, and the aryl group maybe substituted by one to three groups selected from among the aboveC₁-C₆ alkyl group, the above C₁-C₆ alkanoyl, hydroxyl, nitro, cyano,halogen atoms, the above C₂-C₆ alkenyl, the above C₂-C₆ alkynyl, theabove C₁-C₆ halogenoalkyl, the above C₁-C₆ alkoxy, carboxy, carbamoyl,the above C₁-C₆ alkoxycarbonyl, and other groups. Examples of thearalkyl group include a group corresponding to the above C₁-C₆ alkylgroup which has been substituted by one of the C₆-C₁₄ aryl groups (e.g.,benzyl, phenethyl). It should be noted that, in the above description,no particular limitation is imposed on the position of the substitution.

Examples of the acylamino group which may have a substituent include agroup corresponding to the above C₁-C₆ acyl which has been substitutedby an amino group (e.g., formylamino and acetylamino) and also includean acyl group which has been substituted by a single or a plurality ofgroups such as halogen atoms, hydroxyl, C₁-C₆ alkoxy, amino, N—C₁-C₆alkylamino, N,N-di-C₁-C₆ alkylamino, carboxyl, and C₂-C₆ alkoxycarbonyl(e.g., 2-methoxyacetylamino, 3-aminopropionylamino). Examples of theacylaminoalkyl group include a group corresponding to the above C₁-C₆acylamino group which has been substituted by the above C₁-C₆ alkylgroup (e.g., formylaminomethyl and acetylaminomethyl). Examples of theaminoalkyl group include a group corresponding to the above C₁-C₆ alkylwhich has been substituted by a single amino group (e.g., aminomethyland 1-aminoethyl). Examples of the N-alkylaminoalkyl group include agroup corresponding to an amino-(C₁-C₆ alkyl) group which has beensubstituted by a single C₁-C₆ alkyl group at the nitrogen atom of theamino-C₁-C₆ alkyl group (e.g., N-methylaminomethyl, N-methylaminoethyl).Examples of the N,N-dialkylaminoalkyl group include a groupcorresponding to an amino-(C₁-C₆ alkyl) group which has been substitutedby two C₁-C₆ alkyl groups at the nitrogen atom of theN,N-dialkylaminoalkyl group (e.g., N,N-dimethylaminomethyl andN-ethyl-N-methylaminoethyl). Examples of the N-alkenylcarbamoyl groupinclude a group corresponding to a carbamoyl group which has beensubstituted by a linear or branched C₂-C₆ alkenyl group (e.g.,allylcarbamoyl). Examples of the N-alkenylcarbamoylalkyl group include agroup corresponding to a C₁-C₆ alkyl group which has been substituted bythe above N—(C₂-C₆ alkenyl)carbamoyl group (e.g., allylcarbamoylethyl).Examples of the N-alkenyl-N-alkylcarbamoyl group include a groupcorresponding to the above N—(C₂-C₆ alkenyl)carbamoyl group which hasbeen substituted by a linear or branched C₁-C₆ alkyl group at thenitrogen atom of the N-alkenyl-N-alkylcarbamoyl group (e.g.,N-allyl-N-methylcarbamoyl). Examples of theN-alkenyl-N-alkylcarbamoylalkyl group include a group corresponding tothe above N—(C₂-C₆ alkenyl)carbamoylalkyl group which has beensubstituted by a linear or branched C₁-C₆ alkyl group at the nitrogenatom of the N-alkenyl-N-alkylcarbamoylalkyl group (e.g.,N-allyl-N-methylcarbamoylmethyl). Examples of the N-alkoxycarbamoylgroup include a group corresponding to a carbamoyl group which has beensubstituted by a linear or branched C₁-C₆ alkoxy group (e.g.,methoxycarbamoyl). Examples of the N-alkoxycarbamoylalkyl include agroup corresponding to a linear or branched C₁-C₆ alkyl group which hasbeen substituted by the above N—(C₁-C₆ alkoxy)carbamoyl group (e.g.,methoxycarbamoylmethyl). Examples of the N-alkyl-N-alkoxycarbamoyl groupinclude a group corresponding to a carbamoyl group which has beensubstituted by a linear or branched C₁-C₆ alkoxy and C₁-C₆ alkyl groups(e.g., N-ethyl-N-methoxycarbamoyl). Examples of theN-alkyl-N-alkoxycarbamoylalkyl group include a group corresponding to alinear or branched C₁-C₆ alkyl group which has been substituted by theabove N—(C₁-C₆ alkyl)-N—(C₁-C₆ alkoxy)carbamoyl group (e.g.,N-ethyl-N-methoxycarbamoylmethyl). Examples of the carbazoyl group whichmay be substituted by 1 to 3 alkyl groups a carbazoyl group and a groupcorresponding to a carbazoyl group which has been substituted by 1 to 3linear or branched C₁-C₆ alkyl groups (e.g., 1-methylcarbazoyl and1,2-dimethylcarbazoyl). Examples of the alkylsulfonyl group include alinear, branched, or cyclic C₁-C₆ alkylsulfonyl group (e.g.,methanesulfonyl).

Examples of the alkylsulfonylalkyl group include a group correspondingto a linear or branched C₁-C₆ alkyl group which has been substituted bythe above C₁-C₆ alkylsulfonyl group (e.g., methanesulfonylmethyl).Examples of the alkoxyimino group include a C₁-C₆ alkoxyimino group(e.g., methoxyimino and ethoxyimino). Examples of thealkoxycarbonylalkylamino group include a group corresponding to an aminogroup which has been substituted by one of the above C₁-C₆alkoxycarbonylalkyl groups (e.g., methoxycarbonylmethylamino andethoxycarbonylpropylamino).

Examples of the carboxyalkylamino group include a group corresponding toan amino group which has been substituted by one of the above carboxyC₁-C₆ alkyl groups (e.g., carboxymethylamino and carboxyethylamino).Examples of the alkoxycarbonylamino group include a group correspondingto an amino group which has been substituted by one of the above C₁-C₆alkoxycarbonyl groups (e.g., methoxycarbonylamino andtert-butoxycarbonylamino). Examples of the alkoxycarbonylaminoalkylgroup include a group corresponding to the above alkyl group which hasbeen substituted by one of the above C₁-C₆ alkoxycarbonylamino groups(e.g., methoxycarbonylaminomethyl and tert-butoxycarbonylaminoethyl).

The N-alkylcarbamoyl group whose alkyl may or may not be substituted isa carbamoyl group which has been substituted by a linear, branched, orcyclic C₁-C₆ alkyl group which may be substituted by, for example,hydroxyl, amino, N—C₁-C₆ alkylamino, amidino, halogen atom, carboxyl,cyano, carbamoyl, C₁-C₆ alkoxy, C₁-C₆ alkanoyl, C₁-C₆ alkanoylamino, orC₁-C₆ alkylsulfonylamino. Examples include N-methylcarbamoyl,N-ethylcarbamoyl, N-isopropylcarbamoyl, N-cyclopropylcarbamoyl,N-(2-hydroxyethyl)carbamoyl, N-(2-fluoroethyl)carbamoyl,N-(2-cyanoethyl)carbamoyl, N-(2-methoxyethyl)carbamoyl,N-carboxymethylcarbamoyl, N-(2-aminoethyl)carbamoyl, andN-(2-amidinoethyl)carbamoyl. The N,N-dialkylcarbamoyl group whose alkylsmay or may not be substituted is a carbamoyl group which has beensubstituted by two linear, branched, or cyclic C₁-C₆ alkyl groups whichmay be substituted by, for example, hydroxy, amino, N—C₁-C₆ alkylamino,amidino, halogen atom, carboxyl, cyano, carbamoyl, C₁-C₆ alkoxy, C₁-C₆alkanoyl, C₁-C₆ alkanoylamino, and C₁-C₆ alkylsulfonylamino. Examplesinclude N,N-dimethylcarbamoyl, N,N-diethylcarbamoyl,N-ethyl-N-methylcarbamoyl, N-isopropyl-N-methylcarbamoyl,N-(2-hydroxyethyl)-N-methylcarbamoyl, N,N-bis(2-hydroxyethyl)carbamoyl,N,N-bis(2-fluoroethyl)carbamoyl, N-(2-cyanoethyl)-N-methylcarbamoyl,N-(2-methoxyethyl)-N-methylcarbamoyl, N-carboxymethyl-N-methylcarbamoyl,and N,N-bis(2-aminoethyl)carbamoyl. Examples of theN-alkylcarbamoylalkyl group whose alkyl may or may not be substitutedinclude a group corresponding to a linear or branched C₁-C₆ alkyl groupwhich has been substituted by the above N-alkylcarbamoyl group whoseC₁-C₆ alkyl may or may not be substituted (e.g., N-methylcarbamoylmethyland N-(2-hydroxyethyl)carbamoylmethyl). Examples of theN,N-dialkylcarbamoylalkyl group whose alkyls may or may not besubstituted include a group corresponding to a linear or branched C₁-C₆alkyl group which has been substituted by the above N,N-dialkylcarbamoylgroup whose C₁-C₆ alkyls may or may not be substituted (e.g.,N,N-dimethylcarbamoylmethyl andN-(2-hydroxyethyl)-N-methylcarbamoylmethyl).

Examples of the 3- to 6-membered heterocyclic carbonyl group which mayhave a substituent include a group formed of a carbonyl group and theabove 3- to 6-membered heterocyclic group which may have a substituent(e.g., aziridinylcarbonyl, azetidinylcarbonyl,3-hydroxyazetidinylcarbonyl, 3-methoxyazetidinylcarbonyl,pyrrolidinylcarbonyl, 3-hydroxypyrrolidinylcarbonyl,3-fluoropyrrolidinylcarbonyl, piperidylcarbonyl, piperazinylcarbonyl,morpholinylcarbonyl, thiomorpholinylcarbonyl,1,1-dioxothiomorpholinylcarbonyl, tetrahydropyranylcarbonyl,pyridylcarbonyl, furoyl, and thiophenecarbonyl). Examples of the 3- to6-membered heterocyclic carbonylalkyl group which may have a substituentinclude a group corresponding to the above C₁-C₆ alkyl group which hasbeen substituted by one of the above 3- to 6-membered heterocycliccarbonyl groups which may have a substituent (e.g.,azetidinylcarbonylmethyl and pyrrolidinylcarbonylethyl).

Examples of the 3- to 6-membered heterocyclic carbonyloxyalkyl groupwhich may have a substituent include a group corresponding to the aboveC₁-C₆ alkyl group which has been substituted by one of the 3- to6-membered heterocyclic carbonyloxy groups formed of an oxygen atom andthe above 3- to 6-membered heterocyclic carbonyl group which may have asubstituent (e.g., piperidinylcarbonyloxyethyl andmorpholinylcarbonyloxymethyl). Examples of the carbamoyloxyalkyl groupinclude a group corresponding to the above C₁-C₆ alkyl group which hasbeen substituted by one of the carbamoyloxy groups formed of a carbamoylgroup and an oxygen atom (e.g., carbamoyloxymethyl andcarbamoyloxyethyl). Examples of the N-alkylcarbamoyloxyalkyl groupinclude a group corresponding to the above C₁-C₆ alkyl group which hasbeen substituted by one of the N-alkylcarbamoyloxy groups formed of anoxygen atom and the above N-alkylcarbamoyl group whose C₁-C₆ alkyl mayor may not be substituted (e.g., N-methylcarbamoyloxymethyl andN-methylcarbamoyloxyethyl). Examples of the N,N-dialkylcarbamoyloxyalkylgroup include a group corresponding to the above C₁-C₆ alkyl group whichhas been substituted by one of the N,N-dialkylcarbamoyloxy groups formedof an oxygen atom and the above N,N-dialkylcarbamoyl group whose C₁-C₆alkyls may or may not be substituted (e.g.,N,N-dimethylcarbamoyloxymethyl and N-ethyl-N-methylcarbamoyloxyethyl).

Examples of the alkylsulfonylamino group include a group correspondingto an amino group which has been substituted by one of the abovealkylsulfonyl groups having a C₁-C₆ alkyl group (e.g.,methylsulfonylamino and isopropylsulfonylamino). Examples of thearylsulfonylamino group include a group corresponding to an amino groupwhich has been substituted by one of the above arylsulfonyl groupshaving an aryl group (e.g., phenylsulfonylamino andnaphthylsulfonylamino). Examples of the alkylsulfonylaminoalkyl groupinclude a group corresponding to the above C₁-C₆ alkyl group which hasbeen substituted by one of the above C₁-C₆ alkylsulfonylamino groups(e.g., methylsulfonylaminomethyl and methylsulfonylaminoethyl).

Examples of the arylsulfonylaminoalkyl group include a groupcorresponding to the above C₁-C₆ alkyl group which has been substitutedby one of the above arylsulfonylamino groups (e.g.,phenylsulfonylaminomethyl and naphthylsulfonylaminoethyl). Examples ofthe alkylsulfonylaminocarbonyl group include a group formed of the aboveC₁-C₆ alkylsulfonylamino group and a carbonyl group (e.g.,methylsulfonylaminocarbonyl and isopropylsulfonylaminocarbonyl).Examples of the arylsulfonylaminocarbonyl group include a group formedof the above arylsulfonylamino group and a carbonyl group (e.g.,phenylsulfonylaminocarbonyl and naphthylsulfonylaminocarbonyl). Examplesof the alkylsulfonylaminocarbonylalkyl group include a groupcorresponding to the above C₁-C₆ alkyl group which has been substitutedby the above C₁-C₆ alkylsulfonylaminocarbonyl group (e.g.,methylsulfonylaminocarbonylmethyl andisopropylsulfonylaminocarbonylmethyl). Examples of thearylsulfonylaminocarbonylalkyl group include a group corresponding tothe above C₁-C₆ alkyl group which has been substituted by the abovearylsulfonylaminocarbonyl group (e.g., phenylsulfonylaminocarbonylmethyland naphthyl sulfonylaminocarbonylmethyl). Examples of thealkoxycarbonylalkyloxy group include a group corresponding to the aboveC₁-C₆ alkoxy group which has been substituted by the abovealkoxycarbonyl group (e.g., methoxycarbonylmethyloxy).

The acyloxy group is a group formed of the above acyl group and anoxygen atom (e.g., formyloxy and acetyloxy). Examples of theacyloxyalkyl group include a group corresponding to the above C₁-C₆alkyl group which has been substituted by the above acyloxy group (e.g.,formyloxymethyl and acetyloxymethyl). Examples of the aralkyloxy groupinclude a group corresponding to the above C₁-C₆ alkoxy group which hasbeen substituted by the above aryl group (e.g., benzyloxy andnaphthylmethoxy). Examples of the carboxyalkyloxy group include a groupcorresponding to the above alkoxy group which has been substituted by acarboxyl group (e.g., carboxymethoxy and carboxyethoxy).

Examples of the arylsulfonyl group include a C₆-C₁₄ arylsulfonyl group(e.g., phenylsulfonyl and naphthylsulfonyl). Examples of thealkoxycarbonylalkylsulfonyl group include a group formed of the aboveC₁-C₆ alkoxycarbonylalkyl group and a sulfonyl group (e.g.,methoxycarbonylethylsulfonyl, and ethoxycarbonylethylsulfonyl). Examplesof the carboxyalkylsulfonyl group include a group formed of the abovecarboxyalkyl group and a sulfonyl group (e.g., carboxymethylsulfonyl andcarboxyethylsulfonyl). Examples of the alkoxycarbonylacyl group includea group formed of the above alkoxycarbonylalkyl group and a carbonylgroup (e.g., methoxycarbonylmethylcarbonyl andethoxycarbonylmethylcarbonyl). Examples of the alkoxyalkyloxycarbonylgroup include a group corresponding to the above alkoxycarbonyl groupwhich has been substituted by one of the above C₁-C₆ alkoxy groups(e.g., methoxymethyloxycarbonyl and methoxyethyloxycarbonyl).

Examples of the hydroxyacyl group include a group corresponding to theabove acyl group (including C₁-C₆ alkanoyl and aroyl) which has beensubstituted by one hydroxyl group (e.g., glycoloyl, lactoyl, andbenziloyl). Examples of the alkoxyacyl group include a groupcorresponding to the above acyl group which has been substituted by oneof the above C₁-C₆ alkoxy groups (e.g., methoxyacetyl and ethoxyacetyl).Examples of the halogenoacyl group include a group formed of the abovehalogenoalkyl group and a carbonyl group (e.g., chloromethylcarbonyl andtrifluoromethylcarbonyl). Examples of the carboxyacyl group include agroup corresponding to the above acyl group which has been substitutedby one carboxyl group (e.g., carboxyacetyl and 2-carboxypropionyl).Examples of the aminoacyl group include a group corresponding to theabove acyl group (including C₁-C₆ alkanoyl and aroyl) which has beensubstituted by one amino group (e.g., aminomethylcarbonyl and1-aminoethylcarbonyl). Examples of the acyloxyacyl group include a groupformed of the above acyloxyalkyl group and a carbonyl group (e.g.,formyloxymethylcarbonyl and acetyloxymethylcarbonyl). Examples of theacyloxyalkylsulfonyl group include a group formed of the aboveacyloxyalkyl group and a sulfonyl group (e.g., formyloxymethylsulfonyland acetyloxymethylsulfonyl). Examples of the hydroxyalkylsulfonyl groupinclude a group formed of the above C₁-C₆ hydroxyalkyl group and asulfonyl group (e.g., hydroxymethylsulfonyl and 1-hydroxyethylsulfonyl).Examples of the alkoxyalkylsulfonyl group include a group formed of theabove C₁-C₆ alkoxyalkyl group and a sulfonyl group (e.g.,methoxymethylsulfonyl and ethoxyethylsulfonyl).

Examples of the 3- to 6-membered heterocyclic sulfonyl group which mayhave a substituent include a group formed of a sulfonyl group and theabove 3- to 6-membered heterocyclic ring which may have a substituent(e.g., aziridinylsulfonyl, azetidinylsulfonyl, pyrrolidinylsulfonyl,piperidylsulfonyl, piperazinylsulfonyl, morpholinylsulfonyl, andtetrahydropyranylsulfonyl). Examples of the 3- to 6-memberedheterocyclic oxy group which may have a substituent include a groupformed of an oxygen atom and the above 3- to 6-membered heterocyclicring which may have a substituent (e.g., tetrahydrofuranyloxy). Examplesof the N-alkylaminoacyl include a group corresponding to the aminoacylgroup whose nitrogen atom has been substituted by one of the above C₁-C₆alkyl (e.g., N-methylaminoacetyl and N-ethylaminoacetyl). Examples ofthe N,N-dialkylaminoacyl include a group corresponding to the aboveaminoacyl group whose nitrogen atom has been substituted by two C₁-C₆alkyl groups (e.g., N,N-dimethylaminoacetyl andN-ethyl-N-methylaminoacetyl). Examples of the N,N-dialkylcarbamoylacylgroup whose alkyl groups may or may not be substituted include a groupcorresponding to the above acyl group which has been substituted by theabove N,N-dialkylcarbamoyl group whose C₁-C₆ alkyl groups may or may notbe substituted (e.g., N,N-dimethylcarbamoylacetyl,N,N-diethylcarbamoylacetyl, and N-ethyl-N-methylcarbamoylacetyl).Examples of the N,N-dialkylcarbamoylalkylsulfonyl group whose alkylgroups may or may not be substituted include a group formed of asulfonyl group and the above N,N-dialkylcarbamoyl group whose C₁-C₆alkyl groups may or may not be substituted (e.g.,N,N-dimethylcarbamoylmethylsulfonyl andN-(2-hydroxyethyl)-N-methylcarbamoylmethylsulfonyl). Examples of thealkylsulfonylacyl group include a group corresponding to an acyl groupwhich has been substituted by one of the above alkylsulfonyl grouphaving a C₁-C₆ alkyl group (e.g., methylsulfonylacetyl andisopropylsulfonylacetyl).

Examples of the N-arylcarbamoyl group include a group corresponding to acarbamoyl group which has been substituted by the above aryl group(e.g., phenylcarbamoyl and naphthylcarbamoyl). Examples of the N-(3- to6-membered heterocyclic) carbamoyl group include a group correspondingto a carbamoyl group which has been substituted by the above 3- to6-membered heterocyclic group which may have a substituent (e.g.,pyridylcarbamoyl and thienylcarbamoyl). Examples of theN-alkyl-N-arylcarbamoyl group include a group corresponding to the aboveN-arylcarbamoyl group whose nitrogen atom has been substituted by alinear or branched C₁-C₆ alkyl group (e.g., N-methyl-N-phenylcarbamoyl).Examples of the N-alkyl-N-(3- to 6-membered heterocyclic) carbamoylgroup include a group corresponding to the above N-(3- to 6-memberedheterocyclic) carbamoyl group whose nitrogen atom has been substitutedby a linear or branched C₁-C₆ alkyl group (e.g.,N-methyl-N-thienylcarbamoyl). Examples of the N-arylcarbamoylalkyl groupinclude a group corresponding to a linear or branched C₁-C₆ alkyl groupwhich has been substituted by the above N-arylcarbamoyl group (e.g.,phenylcarbamoylmethyl). Examples of the N-3- to 6-membered heterocycliccarbamoylalkyl group include a group corresponding to a linear orbranched C₁-C₆ alkyl group which has been substituted by the above N-(3-to 6-membered heterocyclic) carbamoyl group (e.g.,pyridylcarbamoylmethyl). Examples of the N-alkyl-N-arylcarbamoylalkylgroup include a group corresponding to the above N-arylcarbamoylalkylgroup whose nitrogen atom has been substituted by a linear or branchedC₁-C₆ alkyl group (e.g., N-methyl-N-phenylcarbamoylmethyl). Examples ofthe N-alkyl-N-(3- to 6-membered heterocyclic) carbamoylalkyl groupinclude a group corresponding to the above N-(3- to 6-memberedheterocyclic) carbamoylalkyl group whose nitrogen atom has beensubstituted by a linear or branched C₁-C₆ alkyl group (e.g.,N-methyl-N-thienylcarbamoylmethyl).

The aminocarbothioyl group is the group represented by —C(═S)—NH₂. TheN-alkylaminocarbothioyl group is an aminothiocarbonyl group which hasbeen substituted by one of the above alkyl groups, such as(methylamino)carbothioyl or (ethylamino)carbothioyl. TheN,N-dialkylaminocarbothioyl group is an aminothiocarbonyl group whichhas been substituted by two of the above alkyl groups, such as(dimethylamino)carbothioyl, or (diethylamino)carbothioyl,(ethylmethylamino)carbothioyl. Examples of the alkylthioalkyl groupinclude a group corresponding to a linear, branched, or cyclic C₁-C₆alkylthio group which has been substituted by a linear, branched, orcyclic C₁-C₆ alkyl group (e.g., methylthiomethyl and 1-methylthioethyl).Examples of the N-acyl-N-alkylaminoalkyl group include a groupcorresponding to an amino-C₁-C₆ alkyl group whose nitrogen atom has beensubstituted by a C₁-C₆ alkyl group (e.g., N-acetyl-N-methylaminomethyl).Examples of the alkoxyalkyl(thiocarbonyl) group is a group formed of theabove alkoxyalkyl group and a thiocarbonyl group, such as2-ethoxyethanethioyl.

The alkylene group is a C1-C5 linear or branched alkylene group, such asmethylene, ethylene, or propylene. The alkenylene group is a C2-C5alkenylene group having one double bond, such as vinylene orpropenylene. Examples of the alkylenedioxy group include C1-C5alkylenedioxy groups such as methylenedioxy, ethylenedioxy, andpropylenedioxy. The carbonyldioxy group is the group represented by—O—C(═O)—O—. It should be noted that, in the above description, noparticular limitation is imposed on the position of the substitution.

Among these substituents represented by R³ or R⁴, preferred are, forexample, hydrogen atom, hydroxyl, alkyl, alkenyl, alkynyl, halogen atom,halogenoalkyl, amino, hydroxyimino, alkoxyimino, aminoalkyl,N-alkylaminoalkyl, N,N-dialkylaminoalkyl, acyl, acylalkyl, acylaminowhich may have a substituent, acylaminoalkyl, alkoxy, alkoxyalkyl,hydroxyalkyl, carboxyl, carboxyalkyl, alkoxycarbonyl,alkoxycarbonylalkyl, alkoxycarbonylamino, alkoxycarbonylaminoalkyl,carbamoyl, N-alkylcarbamoyl groups whose alkyl group may or may not besubstituted, N,N-dialkylcarbamoyl groups whose alkyl groups may or maynot be substituted, N-alkenylcarbamoyl, N-alkenylcarbamoylalkyl,N-alkenyl-N-alkylcarbamoyl, N-alkenyl-N-alkylcarbamoylalkyl,N-alkoxycarbamoyl, N-alkyl-N-alkoxycarbamoyl, N-alkoxycarbamoylalkyl,N-alkyl-N-alkoxycarbamoylalkyl, carbazoyl groups which may besubstituted by 1 to 3 alkyl groups, alkylsulfonyl, alkylsulfonylalkyl,3- to 6-membered heterocyclic carbonyl groups which may have asubstituent, 3- to 6-membered heterocyclic carbonyloxyalkyl groups whichmay have a substituent, 3- to 6-membered heterocyclic group groups whichmay have a substituent, carbamoylalkyl, carbamoyloxyalkyl,N-alkylcarbamoyloxyalkyl, N,N-dialkylcarbamoyloxyalkyl,N-alkylcarbamoylalkyl groups whose alkyl group may or may not besubstituted, N,N-dialkylcarbamoylalkyl groups whose alkyl groups may ormay not be substituted, alkylsulfonylamino, alkylsulfonylaminoalkyl,oxo, acyloxy, acyloxyalkyl, arylsulfonyl, alkoxycarbonylalkylsulfonyl,carboxyalkylsulfonyl, alkoxycarbonylacyl, carboxyacyl,alkoxyalkyloxycarbonyl, halogenoacyl, N,N-dialkylaminoacyl, acyloxyacyl,hydroxyacyl, alkoxyacyl, alkoxyalkylsulfonyl, N,N-dialkylcarbamoylacyl,N,N-dialkylcarbamoylalkylsulfonyl, alkylsulfonylacyl, aminocarbothioyl,N-alkylaminocarbothioyl, N,N-dialkylaminocarbothioyl, andalkoxyalkyl(thiocarbonyl). In addition, alkylene, alkenylene,alkylenedioxy, carbonyldioxy, and other groups which are formed by R³and R⁴ together are preferred.

Preferred is the case where R³ is a hydrogen atom, and R⁴ is any one ofthe substituents listed above as preferred examples thereof. In thiscase, R⁴ is more preferably a hydrogen atom, hydroxyl, alkyl, halogenatom, hydroxyimino, N-alkylaminoalkyl, N,N-dialkylaminoalkyl, acyl,acylamino groups which may have a substituent, acylaminoalkyl, alkoxy,alkoxyalkyl, hydroxyalkyl, carboxyl, alkoxycarbonyl,alkoxycarbonylalkyl, alkoxycarbonylamino, carbamoyl, N-alkylcarbamoylgroups whose alkyl group may or may not be substituted,N,N-dialkylcarbamoyl groups whose alkyl group may or may not besubstituted, N-alkenylcarbamoyl, N-alkenylcarbamoylalkyl,N-alkenyl-N-alkylcarbamoyl, N-alkenyl-N-alkylcarbamoylalkyl,N-alkoxycarbamoyl, N-alkyl-N-alkoxycarbamoyl,N-alkyl-N-alkoxycarbamoylalkyl, carbazoyl group which may be substitutedby 1 to 3 alkyl groups, alkylsulfonyl, alkylsulfonylalkyl, 3- to6-membered heterocyclic carbonyl group which may have a substituent, 3-to 6-membered heterocyclic carbonyloxyalkyl group which may have asubstituent, 3- to 6-membered heterocyclic group which may have asubstituent, carbamoylalkyl, N,N-dialkylcarbamoyloxyalkyl,N-alkylcarbamoylalkyl group whose alkyl group may or may not besubstituted, N,N-dialkylcarbamoylalkyl group whose alkyl groups may ormay not be substituted, alkylsulfonylamino, alkylsulfonylaminoalkyl,acyloxy, arylsulfonyl, alkoxycarbonylalkylsulfonyl,carboxyalkylsulfonyl, alkoxycarbonylacyl, carboxyacyl,alkoxyalkyloxycarbonyl, halogenoacyl, N,N-dialkylaminoacyl, acyloxyacyl,hydroxyacyl, alkoxyacyl, alkoxyalkylsulfonyl, N,N-dialkylcarbamoylacyl,N,N-dialkylcarbamoylalkylsulfonyl, alkylsulfonylacyl, aminocarbothioyl,N-alkylaminocarbothioyl, N,N-dialkylaminocarbothioyl, andalkoxyalkyl(thiocarbonyl), among others.

Among these groups, as R⁴, more preferred are a hydrogen atom, hydroxyl,alkyl, N,N-dialkylaminoalkyl, acylamino group which may have asubstituent, acylaminoalkyl, alkoxy, alkoxyalkyl, hydroxyalkyl,alkoxycarbonyl, alkoxycarbonylamino, carbamoyl, N-alkylcarbamoyl whosealkyl group may or may not be substituted, N,N-dialkylcarbamoyl whosealkyl groups may or may not be substituted, N-alkenylcarbamoyl,N-alkenylcarbamoylalkyl, N-alkenyl-N-alkylcarbamoyl,N-alkenyl-N-alkylcarbamoylalkyl, N-alkyl-N-alkoxycarbamoyl, carbazoylwhich may be substituted by 1 to 3 alkyl groups, alkylsulfonyl,alkylsulfonylalkyl, 3- to 6-membered heterocyclic carbonyl group whichmay have a substituent, 3- to 6-membered heterocyclic group which mayhave a substituent, N,N-dialkylcarbamoyloxyalkyl, N-alkylcarbamoylalkylwhose alkyl group may or may not be substituted,N,N-dialkylcarbamoylalkyl whose alkyl groups may or may not besubstituted, alkylsulfonylamino, alkylsulfonylaminoalkyl, acyloxy, acyl,alkoxyalkyloxycarbonyl, halogenoacyl, N,N-dialkylaminoacyl, hydroxyacyl,alkoxyacyl, aminocarbothioyl, N-alkylaminocarbothioyl,N,N-dialkylaminocarbothioyl, and alkoxyalkyl(thiocarbonyl), amongothers.

Preferred examples of the substituent of R³ or R⁴ include a hydrogenatom, hydroxyl, methyl, ethyl, isopropyl, N,N-dimethylaminomethyl,N,N-dimethylaminoethyl, N,N-diethylaminomethyl, acetylamino,methoxyacetylamino, acetylaminomethyl, acetylaminoethyl, methoxy,ethoxy, methoxymethyl, methoxyethyl, hydroxymethyl, 2-hydroxyethyl,1-hydroxy-1-methylethyl, methoxycarbonyl, ethoxycarbonyl,methoxycarbonylamino, ethoxycarbonylamino, N-allylcarbamoyl,N-allylcarbamoylmethyl, N-allyl-N-methylcarbamoyl,N-allyl-N-methylcarbamoylmethyl, N-methoxy-N-methylcarbamoyl,N,N-dimethylcarbazoyl, N,N,N′-trimethylcarbazoyl, methanesulfonyl,methanesulfonylmethyl, ethanesulfonylmethyl, N-methylcarbamoyl,N-ethylcarbamoyl, N-propylcarbamoyl, N-isopropylcarbamoyl,N-tert-butylcarbamoyl, N-cyclopropylcarbamoyl,N-cyclopropylmethylcarbamoyl, N-(1-ethoxycarbonylcyclopropyl)carbamoyl,N-(2-hydroxyethyl)carbamoyl, N-(2-fluoroethyl)carbamoyl,N-(2-methoxyethyl)carbamoyl, N-(carboxymethyl)carbamoyl,N-(2-aminoethyl)carbamoyl, N-(2-amidinoethyl)carbamoyl,N,N-dimethylcarbamoyl, N,N-diethylcarbamoyl, N-ethyl-N-methylcarbamoyl,N-isopropyl-N-methylcarbamoyl, N-methyl-N-propylcarbamoyl,N-(2-hydroxyethyl)-N-methylcarbamoyl,N-(2-fluoroethyl)-N-methylcarbamoyl, N,N-bis(2-hydroxyethyl)carbamoyl,N,N-bis(2-fluoroethyl)carbamoyl, N-(2-methoxyethyl)-N-methylcarbamoyl,N-carboxymethyl-N-methylcarbamoyl, N,N-bis(2-aminoethyl)carbamoyl,azetidinocarbonyl, 3-methoxyazetidinocarbonyl,3-hydroxyazetidinocarbonyl, pyrrolidinocarbonyl,3-hydroxypyrrolidinocarbonyl, 3-fluoropyrrolidinocarbonyl,3,4-dimethoxypyrrolidinocarbonyl, piperidinocarbonyl,piperazinocarbonyl, morpholinocarbonyl, (tetrahydropyran-4-yl)carbonyl,benzoyl, pyridylcarbonyl, thiazolyl, 4,5-dihydrothiazolyl, oxazolyl,4,5-dihydroxazolyl, 5-methyloxazolyl, imidazolyl, pyrrolidinyl,3-hydroxypyrrolidinyl, piperidyl, piperazinyl, morpholinyl,thiomorpholinyl, 1,1-dioxothiomorpholinyl, tetrahydropyranyl, pyridyl,1,2,4-oxadiazolyl, 3-methyl-1,2,4-oxadiazolyl,5-methyl-1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl,5-methyl-1,3,4-oxadiazolyl, 5-(trifluoromethyl)-1,3,4-oxadiazolyl,1,3-oxazolyl, 1,3,4-thiadiazolyl, 5-methyl-1,3,4-thiadiazolyl,1,3-oxazolidinyl, N-methylcarbamoylmethyl, N-methylcarbamoylethyl,N-ethylcarbamoylmethyl, N-(2-fluoroethyl)carbamoylmethyl,N-(2-methoxyethyl)carbamoylmethyl, N,N-dimethylcarbamoylmethyl,N,N-dimethylcarbamoylethyl, N-(2-fluoroethyl)-N-methylcarbamoylmethyl,N-(2-methoxyethyl)-N-methylcarbamoylmethyl,N,N-dimethylcarbamoyloxymethyl, 2-(N-ethyl-N-methylcarbamoyloxy)ethyl,methylsulfonylamino, ethylsulfonylamino, methylsulfonylaminomethyl,methylsulfonylaminoethyl, acetyl, propionyl, isobutylyl,2-methoxyethoxycarbonyl, trifluoroacetyl, N,N-dimethylaminoacetyl,N-ethyl-N-methylaminoacetyl, hydroxyacetyl,1,1-dimethyl-2-hydroxyethylcarbonyl, methoxyacetyl,1,1-dimethyl-2-methoxyethylcarbonyl, aminocarbothioyl,(dimethylamino)carbothioyl, and 2-methoxyethanethioyl.

As described above, preferred is the case in which R³ represents ahydrogen atom, and R⁴ is any of the groups listed above as specificexamples or a similar group. In particular, N,N-dialkylcarbamoyl groupwhich may have a substituent on the alkyl group thereof is preferred. Ofthese, N,N-dimethylcarbamoyl is preferred. However, R³ and R⁴ are notlimited to the groups listed above as specific examples thereof.

<Group T¹>

T¹ represents carbonyl, sulfonyl, —C(═O)—C(═O)—N(R′)—,—C(═S)—C(═O)—N(R′)—, —C(═O)—C(═S)—N(R′)—, —C(═S)—C(═S)—N(R′)— (whereinR′ represents a hydrogen atom, hydroxyl, alkyl, or alkoxy),—C(═O)-A¹-N(R″)— (wherein A¹ represents a C1-C5 alkylene group which mayhave a substituent, R″ represents a hydrogen atom, hydroxyl, alkyl, oralkoxy), —C(═O)—NH—, —C(═S)—NH—, —C(═O)—NH—NH—, —C(═O)-A²-C(═O)—(wherein A² represents a single bond or a C1-C5 alkylene group),—C(═O)-A³-C(═O)—NH— (wherein A³ represents a C1-C5 alkylene),—C(═O)—C(═NOR^(a))—N(R^(b))—, —C(═S)—C(═NOR^(a))—N(R^(b))— (whereinR^(a) represents a hydrogen atom, alkyl, or alkanoyl, R^(b) represents ahydrogen atom, hydroxyl, alkyl, or alkoxy), —C(═O)—N═N—, —C(═S)—N═N—,—C(═NOR^(C))—C(═O)—N(R^(d))— (wherein R^(C) represents a hydrogen atom,alkyl, alkanoyl, aryl, or aralkyl, R^(d) represents a hydrogen atom,hydroxyl, alkyl, or alkoxy), —C(═N—N(R^(e))(R^(f)))—C(═O)—N(R^(g))—(wherein R^(e) and R^(f) each independently represents a hydrogen atom,alkyl, alkanoyl, or alkyl(thiocarbonyl), R^(g) represents a hydrogenatom, hydroxyl, alkyl, or alkoxy), —C(═O)—NH—C(═O)—, —C(═S)—NH—C(═O)—,—C(═O)—NH—C(═S)—, —C(═S)—NHC(═S)—, —C(═O)—NH—SO₂—, —SO₂—NH—,—C(═NCN)—NH—C(═O)—, —C(═S)—C(═O)—, or thiocarbonyl.

In the above groups, the C1-C5 alkylene group in A¹, A², or A³ is aC1-C5 linear, branched, or cyclic alkylene group, such as methylene,ethylene, propylene, cyclopropylene, or 1,3-cyclopentylene. In R′, R″,R^(a), R^(b), R^(c), R^(d), R^(e), R^(f), and R^(g), the alkyl group isa C1-C6 linear, branched, or cyclic alkyl group, such as methyl orethyl. The alkoxy group is a C1-C6 linear, branched, or cyclic alkoxygroup, such as methoxy or ethoxy.

In R^(a), R^(c), R^(e), and R^(f), the alkanoyl group is a groupcomposed of a linear, branched, or cyclic C1-C6 alkyl and a carbonylgroup, such as acetyl or propionyl.

In R^(c), the aryl group is a C6-C14 aryl group, such as phenyl ornaphthyl. The aralkyl group is a group corresponding to a C1-C6 linear,branched, or cyclic alkyl group which has been substituted by a C6-C14aryl group, such as benzyl or phenethyl.

T¹ is preferably carbonyl, —C(═O)—C(═O)—N(R′)—, —C(═S)—C(═O)—N(R′)—,—C(═O)—C(═S)—N(R′)—, —C(═S)—C(═S)—N(R′)—, or —C(═O)—CH₂—N(R″)—,particularly preferably carbonyl, —C(═O)—C(═O)—N(R′)—,—C(═S)—C(═O)—N(R′)—, —C(═O)—C(═S)—N(R′)—, or —C(═S)—C(═S)—N(R′)—.

<Groups R¹ and R²>

R¹ and R² each independently represent a hydrogen atom, hydroxyl, alkyl,or alkoxy, preferably a hydrogen atom or alkyl, more preferably ahydrogen atom.

In R¹ and R², the alkyl group is a C1-C6 linear, branched, or cyclicalkyl group, such as methyl or ethyl. The alkoxy group is a C1-C6linear, branched, or cyclic alkoxy group, such as methoxy or ethoxy. Thecase where R¹ and R² each independently represent a hydrogen atom or analkyl group is preferred, and the case where both are hydrogen atoms ismore preferred.

When T¹ is a carbonyl group or a sulfonyl group, and Q¹ is a C1-C8alkylene group or a C2-C8 alkenylene group, Q² is preferably, among theaforementioned 12 groups, any one of the groups (b), (f), (g), (h), (i),(j), (k), and (l) (wherein, in group (f), N denotes that two of thecarbon atoms forming the ring substituted by R¹⁹ are substituted bynitrogen atoms).

When T¹ is a carbonyl group or a sulfonyl group, and Q¹ is a C1-C8alkylene group or a C2-C8 alkenylene group, the substituent(s) of thering containing Q¹ is preferably N-alkylcarbamoyl orN,N-dialkylcarbamoyl.

When T¹ is —C(═O)—C(═O)—N(R′)—, —C(═S)—C(═O)—N(R′)—,—C(═O)—C(═S)—N(R′)—, or —C(═S)—C(═S)—N(R′)—, and Q¹ is a C1-C8 alkylenegroup or a C2-C8 alkenylene group, Q² is preferably any one of thegroups (i), (j), and (k), among the aforementioned 12 groups.

When T¹ is —C(═O)—C(═O)—N(R′)—, —C(═S)—C(═O)—N(R′)—,—C(═O)—C(═S)—N(R′)—, or —C(═S)—C(═S)—N(R′)—, and Q¹ is a C1-C8 alkylenegroup or a C2-C8 alkenylene group, the substituent of the ringcontaining Q¹ is preferably N-alkylcarbamoyl or N,N-dialkylcarbamoyl.

The feature of the compound represented by formula (8) resides in thecombination of T¹ and Q². Generally, the compounds (8) is divided intothe following two types (I) and (II):

(I) T¹ represents carbonyl, sulfonyl, —C(═O)—NH—C(═O)—,—C(═S)—NH—C(═O)—, —C(═O)—NH—C(═S)—, —C(═S)—NHC(═S)—, —C(═O)—NH—SO₂—,—SO₂—NH—, —C(═NCN)—NH—C(═O)—, —C(═S)—C(═O)—, or thiocarbonyl, and

the group containing Q¹ is represented by the following formula:

(wherein Q¹ represents —(CH₂)m-CH₂-A-CH₂—(CH₂)n- (wherein m and n areeach independently 0 or an integer of 1 to 3, and A represents an oxygenatom, nitrogen atom, sulfur atom, —SO—, —SO₂—, —NH—, —O—NH—, —NH—NH—,—S—NH—, —SO—NH—, or SO₂ —NH—); and

(II) T¹ represents —C(═O)—C(═O)—N(R′)—, —C(═S)—C(═O)—N(R′)—,—C(═O)—C(═S)—N(R′)—, —C(═S)—C(═S)—N(R′)— (wherein R′ represents ahydrogen atom, hydroxyl, alkyl, or alkoxy), —C(═O)-A¹-N(R″)— (wherein A¹represents a C1-C5 alkylene group which may have a substituent, R″represents a hydrogen atom, hydroxyl, alkyl, or alkoxy), —C(═O)—NH—,—C(═S)—NH—, —C(═O)—NH—NH—, —C(═O)-A²-C(═O)— (wherein A² represents asingle bond or a C1-C5 alkylene group), —C(═O)-A³-C(═O)—NH— (wherein A³represents a C1-C5 alkylene), —C(═O)—C(═NOR^(a))—N(R^(b))—,—C(═S)—C(═NOR^(a))—N(R^(b))— (wherein R^(a) represents a hydrogen atom,alkyl or alkanoyl, R^(b) represents a hydrogen atom, hydroxyl, alkyl, oralkoxy), —C(═O)—N═N—, C(═S)—N═N—, —C(═NOR^(C))—C(═O)—N(R^(d))— (whereinR^(C) represents a hydrogen atom, alkyl, alkanoyl, aryl, or aralkyl,R^(d) represents a hydrogen atom, hydroxyl, alkyl, or alkoxy),—C(═N—N(R^(e))(R^(f)))—C(═O)—N(R^(g))— (wherein R^(e) and R^(f) eachindependently represents a hydrogen atom, alkyl, alkanoyl, oralkyl(thiocarbonyl), R^(g) represents a hydrogen atom, hydroxyl, alkyl,or alkoxy), —C(═O)—NH—C(═O)—, —C(═S)—NH—C(═O)—, —C(═O)—NH—C(═S)—,—C(═S)—NHC(═S)—, —C(═O)—NH—SO₂—, —SO₂—NH—, —C(═NCN)—NH—C(═O)—,—C(═S)—C(═O)—, or thiocarbonyl; and

the group containing Q¹ is represented by the following formula:

(wherein Q¹ represents a C1-C8 alkylene, C2-C8 alkenylene, or—(CH₂)m-CH₂-A-CH₂—(CH₂)n- (wherein m and n are each independently 0 oran integer of 1 to 3, and A represents an oxygen atom, nitrogen atom,sulfur atom, —SO—, —SO₂—, —NH—, —O—NH—, —NH—NH—, —S—NH—, —SO—NH—, orSO₂—NH—.).

In the above (I) and (II), for example, the following (i) and (ii),respectively, are preferred:

(i) R¹ and R² each independently represents a hydrogen atom or an alkylgroup, Q¹ represents —(CH₂)m-CH₂-A-CH₂—(CH₂)n- (wherein m and n are eachindependently 0 or 1, and A has the same meaning as described above), Q²is, among the aforementioned 12 groups, a group selected from the 9groups (a) to (h), and (l), and T¹ represents a carbonyl group or asulfonyl group; and

(ii) R¹ and R² each independently represents a hydrogen atom or an alkylgroup, Q¹ represents a C3-C6 alkylene group or —(CH₂)m-CH₂-A-CH₂—(CH₂)n-(wherein m and n are each independently 0 or 1, and A has the samemeaning as described above), Q² is, among the aforementioned 12 groups,a group selected from the three groups (i), (j), and (k), and T¹represents —C(═O)—C(═O)—N(R′)—, —C(═S)—C(═O)—N(R′)—,—C(═O)—C(═S)—N(R′)—, or —C(═S)—C(═S)—N(R′)—.

The compound represented by formula (8) may have correspondingstereochemical isomers and optical isomers based on asymmetric carbonatoms. The present invention encompasses any of the stereochemicalisomers, the optical isomers and mixtures thereof.

No particular limitation is imposed on the salt of the compoundrepresented by formula (8), so long as the salt is pharmaceuticallyacceptable. Examples of the salt include mineral acid salts such ashydrochloride, hydrobromide, hydroiodide, phosphate, nitrate, andsulfate, benzoate, organic sulfates such as methanesulfonate,2-hydroxyethanesulfonate, and p-toluenesulfonate, and organiccarboxylates such as acetate, propanoic acid salt, oxalate, malonate,succinate, glutarate, adipate, tartrate, maleate, malate, citrate, andmandelate.

When the compound represented by formula (8) has an acidic group, thecompound may form a salt with an alkali metal ion or alkaline earthmetal ion. The compound represented by formula (8) or a salt thereof mayform a solvate. No particular limitation is imposed on the solvate, solong as the solvate is pharmaceutically acceptable, and examples of thesolvate include hydrates and solvates with ethanol. When the compoundrepresented by formula (8) includes a nitrogen atom, the compound mayform an N-oxide.

The compound represented by formula (8) is particularly preferably anyof the following compounds, a salt thereof, or similar compounds.

1)N-((1R*,2S*)-2-{[(5-chloroindol-2-yl)carbonyl]amino}cyclopropyl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

2)N-((1R*,2S*)-2-{[(5-chloroindol-2-yl)carbonyl]amino}cyclobutyl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

3)N-((1R*,2R*)-2-{[(5-chloroindol-2-yl)carbonyl]amino}cyclopentyl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

4)N-((1R*,2S*)-2-{[(5-chloroindol-2-yl)sulfonyl]amino}cyclohexyl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

5)N-((1R*,2R*)-2-{[(5-chloroindol-2-yl)carbonyl]amino}cyclohexyl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

6)N-((1R*,2S*)-2-{[(5-chloroindol-2-yl)carbonyl]amino}cyclohexyl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

7)N-{(1R*,2S*)-2-[(6-chloro-2-naphthoyl)amino]cyclohexyl}-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

8)N-((1R*,2R*)-2-{[(6-chloro-1-benzothiophen-2-yl)carbonyl]amino}cyclohexyl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

9)N-((1R*,2R*)-2-{[(5-fluoroindol-2-yl)carbonyl]amino}cyclohexyl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

10)N-((1R*,2R*)-2-{[(5-chloro-6-fluoroindol-2-yl)carbonyl]amino}cyclohexyl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

11)N-((1R*,2S*)-2-{[(5-bromoindol-2-yl)carbonyl]amino}cyclohexyl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

12)N-((1R*,2S*)-2-{[(5-ethynylindol-2-yl)carbonyl]amino}cyclohexyl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

13)N-((1R*,2R*)-2-{[(5-chloroindol-2-yl)carbonyl]amino}cycloheptyl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

14)N-((1R*,2S*)-2-{[(5-chloroindol-2-yl)carbonyl]amino}cyclooctyl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

15)N-((1R*,2R*)-2-{[(5-chloroindol-2-yl)carbonyl]amino}-4-methoxycyclopentyl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

16)5-methyl-N-((1R*,2S*)-2-{[(5-methylindol-2-yl)carbonyl]amino}cyclohexyl)-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

17)(1R*,3S*,4R*)-4-{[(5-chloroindol-2-yl)carbonyl]amino}-3-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexanecarboxylicacid ethyl ester

18)(1S,3R,4S)-4-{[(5-chloroindol-2-yl)carbonyl]amino}-3-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexanecarboxylicacid ethyl ester

19)(1R*,3R*,4S*)-3-{[(5-chloroindol-2-yl)carbonyl]amino}-4-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexanecarboxylicacid methyl ester

20)(1R*,3S*,4R*)-3-{[(5-chloroindol-2-yl)carbonyl]amino}-4-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexanecarboxylicacid ethyl ester

21)(1R*,3R*,4S*)-4-{[(5-chloroindol-2-yl)carbonyl]amino}-3-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexanecarboxylicacid methyl ester

22)(1R,3R,4S)-4-{[(5-chloroindol-2-yl)carbonyl]amino}-3-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexanecarboxylicacid methyl ester

23)N-((1R*,2S*,5S*)-5-(aminocarbonyl)-2-{[(5-chloroindol-2-yl)carbonyl]amino}cyclohexyl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

24)(1R*,3S*,4R*)-4-{[(5-chloroindol-2-yl)carbonyl]amino}-3-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexanecarboxylicacid

25)N-{(1R*,2S*,5S*)-2-{[(5-chloroindol-2-yl)carbonyl]amino}-5-[(dimethylamino)carbonyl]cyclohexyl}-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

26)(1S,3R,4S)-4-{[(5-chloroindol-2-yl)carbonyl]amino}-3-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexanecarboxylicacid

27)N-{(1R,2S,5S)-2-{[(5-chloroindol-2-yl)carbonyl]amino}-5-[(cyclopropylamino)carbonyl]cyclohexyl}-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

28)N-[(1R,2S,5S)-2-{[(5-chloroindol-2-yl)carbonyl]amino}-5-(pyrrolidin-1-ylcarbonyl)cyclohexyl]-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

29)N-[(1R*,2S*,5S*)-2-{[(5-chloroindol-2-yl)carbonyl]amino}-5-(4-morpholinylcarbonyl)cyclohexyl]-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

30)N-{(1R,2S,5S)-2-{[(5-chloroindol-2-yl)carbonyl]amino}-5-[(ethylamino)carbonyl]cyclohexyl}-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

31)N-{(1R,2S,5S)-2-{[(5-chloroindol-2-yl)carbonyl]amino}-5-[(dimethylamino)carbonyl]cyclohexyl}-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

32)N-((1R,2S,5S)-2-{[(5-chloroindol-2-yl)carbonyl]amino}-5-{[(2-methoxyethyl)(methyl)amino]carbonyl}cyclohexyl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

33)N-((1R,2S,5S)-2-{[(5-chloroindol-2-yl)carbonyl]amino}-5-{[(2-hydroxyethyl)(methyl)amino]carbonyl}cyclohexyl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

34)N-((1R,2S,5S)-5-(1-azetidinylcarbonyl)-2-{[(5-chloroindol-2-yl)carbonyl]amino}cyclohexyl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

35)N-((1R,2S,5S)-2-{[(5-chloroindol-2-yl)carbonyl]amino}-5-{[(3S)-3-fluoropyrrolidinyl]carbonyl}cyclohexyl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

36)(1R*,3R*,4S*)-3-{[(5-chloroindol-2-yl)carbonyl]amino}-4-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexanecarboxylicacid

37)N-{(1R*,2S*,4S*)-2-{[(5-chloroindol-2-yl)carbonyl]amino}-4-[(dimethylamino)carbonyl]cyclohexyl}-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

38)N-((1R,2S,5S)-2-{[(5-chloroindol-2-yl)carbonyl]amino}-5-{[(3R)-3-hydroxypyrrolidinyl]carbonyl}cyclohexyl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

39)N-((1R*,2S*)-2-{[(5-chloroindol-2-yl)carbonyl]amino}-5,5-dimethoxycyclohexyl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide,N-((1R*,2S*)-2-{[(5-chloroindol-2-yl)carbonyl]amino}-4,4-dimethoxycyclohexyl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

40)N-((1R*,2S*)-2-{[(5-chloroindol-2-yl)carbonyl]amino}-5-oxocyclohexyl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide,N-((1R*,2S*)-2-{[(5-chloroindol-2-yl)carbonyl]amino}-4-oxocyclohexyl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

41)N-[(1R*,2S*)-2-{[(5-chloroindol-2-yl)carbonyl]amino}-5-(hydroxyimino)cyclohexyl]-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide,N-[(1R*,2S*)-2-{[(5-chloroindol-2-yl)carbonyl]amino}-4-(hydroxyimino)cyclohexyl]-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

42)N-((7R*,8S*)-8-{[(5-chloroindol-2-yl)carbonyl]amino}-1,4-dioxaspiro[4.5]dec-7-yl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide,N-((7R*,8S*)-7-{[(5-chloroindol-2-yl)carbonyl]amino}-1,4-dioxaspiro[4.5]dec-8-yl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

43)N-[(1R*,2S*)-2-{[(5-chloroindol-2-yl)carbonyl]amino}-5-(methoxyimino)cyclohexyl]-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide,N-[(1R*,2S*)-2-{[(5-chloroindol-2-yl)carbonyl]amino}-4-(methoxyimino)cyclohexyl]-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

44)N-((1R*,2S*)-2-{[(5-chloroindol-2-yl)carbonyl]amino}-5-hydroxycyclohexyl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide,N-((1R*,2S*)-2-{[(5-chloroindol-2-yl)carbonyl]amino}-4-hydroxycyclohexyl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

45)N-((1R*,2S*)-2-{[(5-chloroindol-2-yl)carbonyl]amino}-5-hydroxy-5-methylcyclohexyl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide,N-((1R*,2S*)-2-{[(5-chloroindol-2-yl)carbonyl]amino}-4-hydroxy-4-methylcyclohexyl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

46)N-[(1R*,2R*,5S*)-2-{[(5-chloroindol-2-yl)carbonyl]amino}-5-(hydroxymethyl)cyclohexyl]-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

47)N-[(1R*,2S*,5S*)-2-{[(5-chloroindol-2-yl)carbonyl]amino}-5-(methoxymethyl)cyclohexyl]-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

48)N-((1R*,2S*,5S*)-2-{[(5-chloroindol-2-yl)carbonyl]amino}-5-{[(methylsulfonyl)amino]methyl}cyclohexyl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

49)N-{(1R*,2S*,5S*)-2-{[(5-chloroindol-2-yl)carbonyl]amino}-5-[(dimethylamino)methyl]cyclohexyl}-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

50)(3R*,4S*)-4-{[(5-chloroindol-2-yl)carbonyl]amino}-3-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexylcarbamicacid tert-butyl ester,(3R*,4S*)-3-{[(5-chloroindol-2-yl)carbonyl]amino}-4-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexylcarbamicacid tert-butyl ester

51)N-((1R*,2S*)-5-amino-2-{[(5-chloroindol-2-yl)carbonyl]amino}cyclohexyl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide,N-((1R*,2S*)-4-amino-2-{[(5-chloroindol-2-yl)carbonyl]amino}cyclohexyl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

52)N-[(1R*,2S*)-2-{[(5-chloroindol-2-yl)carbonyl]amino}-5-[(methylsulfonyl)amino]cyclohexyl}-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide,N-[(1R*,2S*)-2-{[(5-chloroindol-2-yl)carbonyl]amino}-4-[methylsulfonyl)amino]cyclohexyl}-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

53)N-((1R*,2S*)-5-(acetylamino)-2-{[(5-chloroindol-2-yl)carbonyl]amino}cyclohexyl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide,N-((1R*,2S*)-4-(acetylamino)-2-{[(5-chloroindol-2-yl)carbonyl]amino}cyclohexyl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

54)N-((1R,2S,5S)-2-{[(5-chloroindol-2-yl)carbonyl]amino}-5-{[methoxy(methyl)amino]carbonyl}cyclohexyl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

55)N-{(1R,2S,5S)-2-{[(5-chloroindol-2-yl)carbonyl]amino}-5-[(2,2-dimethylhydrazino)carbonyl]cyclohexyl}-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

56)6-chloro-N-((1S,2R,4S)-4-[(dimethylamino)carbonyl]-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)-2-quinolinecarboxamide

57) N-{(1R,2S,5S)-2-{[(5-chloro-4-fluoroindol-2-yl)carbonyl]amino}-5-[(dimethylamino)carbonyl]cyclohexyl}-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

58)7-chloro-N-((1S,2R,4S)-4-[(dimethylamino)carbonyl]-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)isoquinoline-3-carboxamide

59)N-((3R*,4S*)-4-{[(5-chloroindol-2-yl)carbonyl]amino}tetrahydrofuran-3-yl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

60)N-((3S,4S)-4-{[(5-chloroindol-2-yl)carbonyl]amino}tetrahydrofuran-3-yl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

61)N-((3R,4R)-4-{[(5-chloroindol-2-yl)carbonyl]amino}tetrahydrofuran-3-yl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

62)(3R,4R)-3-{[(5-chloroindol-2-yl)carbonyl]amino}-4-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}pyrrolidine-1-carboxylicacid tert-butyl ester

63)N-((3R,4R)-4-{[(5-chloroindol-2-yl)carbonyl]amino}pyrrolidin-3-yl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

64)N-((3S,4S)-4-{[(5-chloroindol-2-yl)carbonyl]amino}-5-oxotetrahydrofuran-3-yl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

65)N-((3S,4S)-4-{[(5-chloroindol-2-yl)carbonyl]amino}-2-oxotetrahydrofuran-3-yl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

66)(3S,4R)-2-(3-{[(5-chloroindol-2-yl)carbonyl]amino}-4-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}-2-oxopyrrolidin-1-yl)aceticacid ethyl ester

67)N-((3R,4S)-4-{[(5-chloroindol-2-yl)carbonyl]amino}-1-methyl-5-oxopyrrolidin-3-yl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

68)2-[((3R,4R)-3-{[(5-chloroindol-2-yl)carbonyl]amino}-4-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}pyrrolidin-1-yl)sulfonyl]aceticacid methyl ester

69)2-[((3R,4R)-3-{[(5-chloroindol-2-yl)carbonyl]amino}-4-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}pyrrolidin-1-yl)sulfonyl]aceticacid

70)2-((3R,4R)-3-{[(5-chloroindol-2-yl)carbonyl]amino}-4-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}pyrrolidin-1-yl)aceticacid methyl ester

71)2-(3R,4R)-3-{[(5-chloroindol-2-yl)carbonyl]amino}-4-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}pyrrolidin-1-yl)aceticacid

72)3-((3R,4R)-3-{[(5-chloroindol-2-yl)carbonyl]amino}-4-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}pyrrolidin-1-yl)propionicacid methyl ester

73)3-((3R,4R)-3-{[(5-chloroindol-2-yl)carbonyl]amino}-4-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}pyrrolidin-1-yl)propionicacid

74)3-((3R,4R)-3-{[(5-chloroindol-2-yl)carbonyl]amino}-4-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}pyrrolidin-1-yl)-3-oxopropionicacid ethyl ester

75)3-((3R,4R)-3-{[(5-chloroindol-2-yl)carbonyl]amino}-4-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}pyrrolidin-1-yl)-3-oxopropionicacid

76)1-[((3R,4R)-3-{[(5-chloroindol-2-yl)carbonyl]amino}-4-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}pyrrolidin-1-yl)methyl]cyclopropanecarboxylicacid methyl ester

77)1-[((3R,4R)-3-{[(5-chloroindol-2-yl)carbonyl]amino}-4-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}pyrrolidin-1-yl)methyl]cyclopropanecarboxylicacid

78)(3R*,4S*)-4-{[(5-chloroindol-2-yl)carbonyl]amino}-3-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}piperidine-1-carboxylicacid tert-butyl ester

79)N-((3R*,4S*)-4-{[(5-chloroindol-2-yl)carbonyl]amino}piperidin-3-yl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

80)(3R*,4S*)-3-{[(5-chloroindol-2-yl)carbonyl]amino}-4-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}piperidine-1-carboxylicacid tert-butyl ester

81)N-((3R*,4S*)-3-{[(5-chloroindol-2-yl)carbonyl]amino}piperidin-4-yl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

82)(3R*,4S*)-4-{[(5-fluoroindol-2-yl)carbonyl]amino}-3-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}piperidine-1-carboxylicacid tert-butyl ester

83)N-((3R*,4S*)-4-{[(5-fluoroindol-2-yl)carbonyl]amino}piperidin-3-yl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

84)N-((3R*,4S*)-1-acetyl-4-{[(5-chloroindol-2-yl)carbonyl]amino}piperidin-3-yl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

85)N-((3R*,4S*)-1-acetyl-3-{[(5-chloroindol-2-yl)carbonyl]amino}piperidin-4-yl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

86)N-((3R*,4S*)-1-acetyl-4-{[(5-fluoroindol-2-yl)carbonyl]amino}piperidin-3-yl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

87)N-[(3R*,4S*)-4-{[(5-chloroindol-2-yl)carbonyl]amino}-1-(methylsulfonyl)piperidin-3-yl]-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

88)N-[(3R*,4S*)-3-{[(5-chloroindol-2-yl)carbonyl]amino}-1-(methylsulfonyl)piperidin-4-yl]-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

89)N-[(3R*,4S*)-4-{[(5-fluoroindol-2-yl)carbonyl]amino}-1-(methylsulfonyl)piperazin-3-yl]-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

90)(3R*,4S*)-4-{[(5-chloroindol-2-yl)carbonyl]amino}-3-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}piperidine-1-carboxylicacid methyl ester

91)(3R*,4S*)-4-{[(5-chloroindol-2-yl)carbonyl]amino}-3-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}piperidine-1-carboxylicacid ethyl ester

92)(3R*,4S*)-4-{[(5-chloroindol-2-yl)carbonyl]amino}-3-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}piperidine-1-carboxylicacid 2-methoxyethyl ester

93)(3R*,4S*)-3-{[(5-chloroindol-2-yl)carbonyl]amino}-4-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}piperidine-1-carboxylicacid ethyl ester

94)N-((3R*,4S*)-4-{[(5-chloroindol-2-yl)carbonyl]amino}-1-propionylpiperidin-3-yl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

95)N-((3R*,4S*)-4-{[(5-chloroindol-2-yl)carbonyl]amino}-1-isobutylylpiperidin-3-yl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

96)N-[(3R*,4S*)-4-{[(5-chloroindol-2-yl)carbonyl]amino}-1-(2,2-dimethylpropanoyl)piperidin-3-yl]-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

97)N-[(3R*,4S*)-4-{[(5-chloroindol-2-yl)carbonyl]amino}-1-(3,3-dimethylbutanoyl)piperidin-3-yl]-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

98)N-[(3R*,4S*)-4-{[(5-chloroindol-2-yl)carbonyl]amino}-1-(2,2,2-trifluoroacetyl)piperidin-3-yl]-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

99)N-[(3R*,4S*)-4-{[(5-chloroindol-2-yl)carbonyl]amino}-1-(cyclopropylcarbonyl)piperidin-3-yl]-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

100)N-[(3R*,4S*)-4-{[(5-chloroindol-2-yl)carbonyl]amino}-1-(cyclobutylcarbonyl)piperidin-3-yl]-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

101)N-[(3R*,4S*)-4-{[(5-chloroindol-2-yl)carbonyl]amino}-1-(cyclopentylcarbonyl)piperidin-3-yl]-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

102)2-((3R*,4S*)-4-{[(5-chloroindol-2-yl)carbonyl]amino}-3-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}piperidin-1-yl)-2-oxoethylacetate

103)N-((3R*,4S*)-4-{[(5-chloroindol-2-yl)carbonyl]amino}-1-glycoloylpiperidin-3-yl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

104)N-[(3R*,4S*)-4-{[(5-chloroindol-2-yl)carbonyl]amino}-1-(2-methoxyacetyl)piperidin-3-yl]-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

105)N-[(3R*,4S*)-4-{[(5-fluoroindol-2-yl)carbonyl]amino}-1-(2-methoxyacetyl)piperidin-3-yl]-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

106)N-((3R*,4S*)-1-(3-{[tert-butyl(diphenyl)silyl]oxy}-2,2-dimethylpropanoyl)-4-{[(5-chloroindol-2-yl)carbonyl]amino}piperidin-3-yl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

107)N-[(3R*,4S*)-4-{[(5-chloroindol-2-yl)carbonyl]amino}-1-(3-hydroxy-2,2-dimethylpropanoyl)piperidin-3-yl]-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

108)N-[(3R*,4S*)-4-{[(5-chloroindol-2-yl)carbonyl]amino}-1-(3-methoxy-2,2-dimethylpropanoyl)piperidin-3-yl]-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

109)2-((3R*,4S*)-4-{[(5-chloroindol-2-yl)carbonyl]amino}-3-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}piperidin-1-yl)-1,1-dimethyl-2-oxoethylacetate

110)N-[(3R*,4S*)-4-{[(5-chloroindol-2-yl)carbonyl]amino}-1-(2-methylpropanoyl)piperidin-3-yl]-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

111)N-{(3R*,4S*)-4-{[(5-chloroindol-2-yl)carbonyl]amino}-1-[(3-hydroxycyclobutyl)carbonyl]piperidin-3-yl}-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

112)N-{(3R*,4S*)-4-{[(5-chloroindol-2-yl)carbonyl]amino}-1-[(methoxycyclobutyl)carbonyl]piperidin-3-yl}-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

113)N-{(3R*,4S*)-4-{[(5-chloroindol-2-yl)carbonyl]amino}-1-[3-methoxy-2-(methoxymethyl)propanoyl]piperidin-3-yl}-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

114)N-[(3R*,4S*)-4-{[(5-chloroindol-2-yl)carbonyl]amino}-1-(tetrahydro-2H-pyran-4-ylcarbonyl)piperidin-3-yl]-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

115)N-((3R*,4S*)-1-benzoyl-4-{[(5-chloroindol-2-yl)carbonyl]amino}piperidin-3-yl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

116)N-{(3R*,4S*)-4-{[(5-chloroindol-2-yl)carbonyl]amino}-1-[(dimethylamino)carbonyl]piperidin-3-yl}-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

117)N-{(3R*,4S*)-4-{[(5-chloroindol-2-yl)carbonyl]amino}-1-[(ethylamino)carbonyl]piperidin-3-yl}-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

118)N-((3R*,4S*)-1-[(tert-butylamino)carbonyl]-4-{[(5-chloroindol-2-yl)carbonyl]amino}piperidin-3-yl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

119)2-((3R*,4S*)-4-{[(5-chloroindol-2-yl)carbonyl]amino}-3-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}piperidin-3-yl)aceticacid methyl ester

120)2-((3R*,4S*)-4-{[(5-chloroindol-2-yl)carbonyl]amino}-3-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}piperidin-3-yl)aceticacid

121)N-[(3R*,4S*)-4-{[(5-chloroindol-2-yl)carbonyl]amino}-1-(2-methoxyethyl)piperidin-3-yl]-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

122)N-[(3R*,4S*)-4-{[(5-chloroindol-2-yl)carbonyl]amino}-1-(2-fluoroethyl)piperidin-3-yl]-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

123)N-((3R,4S)-1-acetyl-4-{[(5-chloroindol-2-yl)carbonyl]amino}piperidin-3-yl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

124)N-((3R,4R)-1-acetyl-4-{[(5-chloroindol-2-yl)carbonyl]amino}piperidin-3-yl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

125)N-[(3R,4S)-4-{[(5-chloroindol-2-yl)carbonyl]amino}-1-(2-methoxyacetyl)piperidin-3-yl]-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

126)N-[(3R,4R)-4-{[(5-chloroindol-2-yl)carbonyl]amino}-1-(2-methoxyacetyl)piperidin-3-yl]-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

127)N-((3R,4R)-4-{[(5-chloroindol-2-yl)carbonyl]amino}-6-oxotetrahydro-2H-pyran-3-yl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

128)N-((3R,4S)-4-{[(5-chloroindol-2-yl)carbonyl]amino}-6-oxotetrahydro-2H-pyran-3-yl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

129)(3R,4S)-5-{[tert-butyl(diphenyl)silyl]oxy}-3-{[(5-chloroindol-2-yl)carbonyl]amino}-4-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}valericacid ethyl ester

130)(3R,4S)-3-{[(5-chloroindol2-yl)carbonyl]amino}-5-hydroxy-4-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}valericacid ethyl ester

131)N-((3S,4R)-4-{[(5-chloroindol-2-yl)carbonyl]amino}-6-oxotetrahydro-2H-pyran-3-yl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

132)N-((3R*,4R*)-4-{[(5-chloroindol-2-yl)carbonyl]amino}-1,1-dioxohexahydro-1-thiopyran-3-yl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

133)N-((3R*,4R*)-4-{[(5-fluoroindol-2-yl)carbonyl]amino}-1,1-dioxohexahydro-1-thiopyran-3-yl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

134)N-((3R*,4R*)-3-{[(5-chloroindol-2-yl)carbonyl]amino}-1,1-dioxohexahydro-1-thiopyran-4-yl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

135)N-((3R*,4S*)-4-{[(5-chloroindol-2-yl)carbonyl]amino}-1,1-dioxohexahydro-1-thiopyran-3-yl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

136)N-((3R*,4S*)-4-{[(5-fluoroindol-2-yl)carbonyl]amino}-1,1-dioxohexahydro-1-thiopyran-3-yl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

137)N-((3R*,4R*)-3-{[(5-fluoroindol-2-yl)carbonyl]amino}-1,1-dioxohexahydro-1-thiopyran-4-yl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

138)N-((3S,4R)-4-{[(5-chloroindol-2-yl)carbonyl]amino}-1-methyl-6-oxopiperidin-3-yl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide,N-((3R,4R)-4-{[(5-chloroindol-2-yl)carbonyl]amino}-1-methyl-6-oxopiperidin-3-yl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

139)N¹-(4-chlorophenyl)-N²-((1S,2R,4S)-4-[(dimethylamino)carbonyl]-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)ethanediamide

140)N¹-(5-chloropyridin-2-yl)-N²-((1S,2R,4S)-4-[(dimethylamino)carbonyl]-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)ethanediamide

141)N¹-(3-chlorophenyl)-N²-((1S,2R,4S)-4-[(dimethylamino)carbonyl]-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)ethanediamide

142)N¹-((1S,2R,4S)-4-[(dimethylamino)carbonyl]-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)-N²-(4-fluorophenyl)ethanediamide

143)N¹-(4-bromophenyl)-N²-((1S,2R,4S)-4-[(dimethylamino)carbonyl]-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)ethanediamide

144)N¹-(4-chloro-2-methylphenyl)-N²-((1S,2R,4S)-4-[(dimethylamino)carbonyl]-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)ethanediamide

145)N¹-(4-chloro-3-methylphenyl)-N²-((1S,2R,4S)-4-[(dimethylamino)carbonyl]-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)ethanediamide

146)N¹-(4-chloro-2-fluorophenyl)-N²-((1S,2R,4S)-4-[(dimethylamino)carbonyl]-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)ethanediamide

147)N¹-(2,4-dichlorophenyl)-N²-((1S,2R,4S)-4-[(dimethylamino)carbonyl]-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)ethanediamide

148)N¹-(3,4-dichlorophenyl)-N²-((1S,2R,4S)-4-[(dimethylamino)carbonyl]-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)ethanediamide

149)N¹-(2,4-difluorophenyl)-N²-((1S,2R,4S)-4-[(dimethylamino)carbonyl]-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)ethanediamide

150)N¹-(3,4-difluorophenyl)-N²-((1S,2R,4S)-4-[(dimethylamino)carbonyl]-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)ethanediamide

151)N¹-((1S,2R,4S)-4-[(dimethylamino)carbonyl]-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)-N²-(pyridin-4-yl)ethanediamide

152)N¹-(5-bromopyridin-2-yl)-N²-((1S,2R,4S)-4-[(dimethylamino)carbonyl]-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)ethanediamide

153)N¹-(6-chloropyridin-3-yl)-N²-((1S,2R,4S)-4-[(dimethylamino)carbonyl]-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)ethanediamide

154)N¹-(6-chloropyridazin-3-yl)-N²-((1S,2R,4S)-4-[(dimethylamino)carbonyl]-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)ethanediamide

155)N¹-(5-chlorothiazol-2-yl)-N²-((1S,2R,4S)-4-[(dimethylamino)carbonyl]-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)ethanediamide

156)N-{(1R,2S,5S)-2-{[2-(4-chloroanilino)acetyl]amino}-5-[(dimethylamino)carbonyl]cyclohexyl}-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

157)N-{(1R,2S,5S)-2-{[2-(4-chloro-2-fluoroanilino)acetyl]amino}-5-[(dimethylamino)carbonyl]cyclohexyl}-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

158)N-{(1R,2S,5S)-2-{[(5-chloro-4-fluoroindol-2-yl)carbonyl]amino}-5-[(dimethylamino)carbonyl]cyclohexyl}-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

159)N-{(1R,2S,5S)-2-{[(5-chloro-3-fluoroindol-2-yl)carbonyl]amino}-5-[(dimethylamino)carbonyl]cyclohexyl}-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

160)N-{(1R,2S,5S)-2-{[(3-bromo-5-chloroindol-2-yl)carbonyl]amino}-5-[(dimethylamino)carbonyl]cyclohexyl}-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

161)N-{(1R,2S,5S)-2-{[(3-chloro-5-fluoroindol-2-yl)carbonyl]amino}-5-[(dimethylamino)carbonyl]cyclohexyl}-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

162)N-{(1R,2S,5S)-2-{[(5-chloro-3-formylindol-2-yl)carbonyl]amino}-5-[(dimethylamino)carbonyl]cyclohexyl}-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

163)5-chloro-N²-((1S,2R,4S)-4-[(dimethylamino)carbonyl]-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)-N³,N³-dimethylindole-2,3-dicarboxamide

164)N-{(1R,2S,5S)-2-[(6-chloro-2-naphthoyl)amino]-5-[(dimethylamino)carbonyl]cyclohexyl}-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

165)7-chloro-N-((1S,2R,4S)-4-[(dimethylamino)carbonyl]-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)cinnoline-3-carboxamide

166)N-{(1R,2S,5S)-2-{[(5-chlorobenzimidazol-2-yl)carbonyl]amino}-5-[(dimethylamino)carbonyl]cyclohexyl}-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

167)N-((1S,2R,4S)-4-[(dimethylamino)carbonyl]-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)-7-fluoroisoquinoline-3-carboxamide

168)N-{(1R,2S,5S)-2-{[(7-chloro-2H-chromen-3-yl)carbonyl]amino}-5-[(dimethylamino)carbonyl]cyclohexyl}-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

169)N-{(1R,2S,5S)-2-{[(E)-3-(4-chlorophenyl)-2-propenoyl]amino}-5-[(dimethylamino)carbonyl]cyclohexyl}-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

170)6-chloro-N-((1S,2R,4S)-4-[(dimethylamino)carbonyl]-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)-4-oxo-1,4-dihydroquinoline-2-carboxamide

171)7-chloro-N-((1S,2R,4S)-4-{[ethyl(methyl)amino]carbonyl}-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)isoquinoline-3-carboxamide

172)N-{(1R*,2S*,5S*)-2-{[(5-chloroindol-2-yl)carbonyl]amino}-5-[2-(dimethylamino)-2-oxoethyl]cyclohexyl}-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

173)N-{(1R,2S,5S)-2-{[(5-chloroindol-2-yl)carbonyl]amino}-5-[(methylsulfonyl)methyl]cyclohexyl}-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

174)N-{(1R,2S,5S)-2-{[(2-chloro-6H-thieno[2,3-b]pyrrol-5-yl)carbonyl]amino}-5-[(dimethylamino)carbonyl]cyclohexyl}-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

175)N-{(1R,2S,5S)-2-{[3-(4-chlorophenyl)-2-propynoyl]amino}-5-[(dimethylamino)carbonyl]cyclohexyl}-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

176)6-chloro-N-((1S,2R,4S)-4-[(dimethylamino)carbonyl]-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)-4-oxo-1,4-dihydroquinazoline-2-carboxamide

177)N-{(1R,2S,5S)-2-{[2-(4-chloroanilino)-2-oxoethanethioyl]amino}-5-[(dimethylamino)carbonyl]cyclohexyl}-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

178)N-{(1R,2S,5S)-2-({2-[(5-chloropyridin-2-yl)amino]-2-oxoethanethioyl}amino)-5-[(dimethylamino)carbonyl]cyclohexyl}-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

179)N-{(1R,2S,5S)-2-({2-[(5-chloropyridin-2-yl)amino]-2-thioxoacetyl}amino)-5-[(dimethylamino)carbonyl]cyclohexyl}-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

180)N¹-(5-chloro-2-thienyl)-N²-((1S,2R,4S)-4-[(dimethylamino)carbonyl]-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)ethanediamide

181)N-{(1R,2S,5S)-2-{[(4-chloroanilino)carbonyl]amino}-5-[(dimethylamino)carbonyl]cyclohexyl}-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

182)N¹-((1S,2R,4S)-4-[(dimethylamino)carbonyl]-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)-N²-(5-fluoropyridin-2-yl)ethanediamide

183)N¹-[4-chloro-2-(trifluoromethyl)phenyl]-N²-((1S,2R,4S)-4-[(dimethylamino)carbonyl]-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)ethanediamide

184)N¹-{4-chloro-2-[(dimethylamino)carbonyl]phenyl}-N²-((1S,2R,4S)-4-[(dimethylamino)carbonyl]-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)ethanediamide

185)N¹-[4-chloro-2-(hydroxymethyl)phenyl]-N²-((1S,2R,4S)-4-[(dimethylamino)carbonyl]-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)ethanediamide

186)N¹-(4-chloro-2-methoxyphenyl)-N²-((1S,2R,4S)-4-[(dimethylamino)carbonyl]-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)ethanediamide

187)N-{(1R,2S,5S)-2-{[2-(4-chloroanilino)-2-(hydroxyimino)acetyl]amino}-5-[(dimethylamino)carbonyl]cyclohexyl}-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

188)N¹-(4-chlorophenyl)-N²-((3R,4S)-1-(2-methoxyacetyl)-3-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}piperidin-4-yl)ethanediamide

189)N¹-(5-chloropyridin-2-yl)-N²-((3R,4S)-1-(2-methoxyacetyl)-3-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}piperidin-4-yl)ethanediamide

190)N¹-(5-bromopyridin-2-yl)-N²-((3R,4S)-1-(2-methoxyacetyl)-3-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}piperidin-4-yl)ethanediamide

191)N¹-(4-chlorophenyl)-N³-((1S,2R,4S)-4-[(dimethylamino)carbonyl]-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)malonamide

192)N¹-(3-chlorophenyl)-N³-((1S,2R,4S)-4-[(dimethylamino)carbonyl]-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)malonamide

193)N¹-(5-chloropyridin-2-yl)-N²-((1S,2R,4S)-4-{[ethyl(methyl)amino]carbonyl}-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)ethanediamide

194)N¹-(4-chlorophenyl)-N²-((1S,2R,4S)-4-{[ethyl(methyl)amino]carbonyl}-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)ethanediamide

195)N¹-(5-bromopyridin-2-yl)-N²-((1S,2R,4S)-4-{[ethyl(methyl)amino]carbonyl}-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)ethanediamide

196)N¹-(4-chloro-3-fluorophenyl)-N²-((1S,2R,4S)-4-[(dimethylamino)carbonyl]-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)ethanediamide

197)N-{(1R,2S,5S)-2-{[3-(4-chlorophenyl)-3-oxopropanoyl]amino}-5-[(dimethylamino)carbonyl]cyclohexyl}-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

198)N¹-[(5-chloropyridin-2-yl)amino]-N²-((1R,2R,4S)-4-[(dimethylamino)carbonyl]-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)ethanediamide

199)N¹-(4-chlorophenyl)-N²-((1R,2R,4S)-4-[(dimethylamino)carbonyl]-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)ethanediamide

200)N¹-(5-chloropyridin-2-yl)-N²-((1S,2R,4S)-4-[(dimethylamino)carbonyl]-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)-N¹-methylethanediamide

201)N¹-(5-chloropyrimidin-2-yl)-N²-((1S,2R,4S)-4-[(dimethylamino)carbonyl]-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)ethanediamide

202)N¹-(4-chloro-3-methoxyphenyl)-N²-((1S,2R,4S)-4-[(dimethylamino)carbonyl]-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)ethanediamide

203)N¹-(4-chlorophenyl)-N²-((1R*,2R*)-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclopentyl)ethanediamide

204)N¹-(5-chloropyridin-2-yl)-N²-((1R*,2R*)-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclopentyl)ethanediamide

205)N¹-((1S,2R,4S)-4-[(dimethylamino)carbonyl]-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)-N²-(4-ethynylphenyl)ethanediamide

206)N¹-(5-chloropyrazin-2-yl)-N²-((1S,2R,4S)-4-[(dimethylamino)carbonyl]-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)ethanediamide

207)N¹-(4-chloro-3-nitrophenyl)-N²-((1S,2R,4S)-4-[(dimethylamino)carbonyl]-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)ethanediamide

208)N¹-(4-chloro-2-nitrophenyl)-N²-((1S,2R,4S)-4-[(dimethylamino)carbonyl]-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)ethanediamide

209)N¹-(3-amino-4-chlorophenyl)-N²-((1S,2R,4S)-4-[(dimethylamino)carbonyl]-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)ethanediamide

210)N¹-(2-amino-4-chlorophenyl)-N²-((1S,2R,4S)-4-[(dimethylamino)carbonyl]-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)ethanediamide

211)N¹-(6-chloro-4-methylpyridin-3-yl)-N²-((1S,2R,4S)-4-[(dimethylamino)carbonyl]-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)ethanediamide

212)N-{(1R,2S,5S)-2-({[(E)-2-(4-chlorophenyl)diazenyl]carbonyl}amino)-5-[(dimethylamino)carbonyl]cyclohexyl}-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

213)N-{(1R,2S,5S)-2-({[2-(4-chlorophenyl)hydrazino]carbonyl}amino)-5-[(dimethylamino)carbonyl]cyclohexyl}-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

214)N¹-(5-chloropyridin-2-yl)-N²-((1S,2R,4S)-4-[(dimethylamino)carbonyl]-2-{[(4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)ethanediamide

215)N-{(3R*,4S*)-4-{[(5-chloroindol-2-yl)carbonyl]amino}-1-[(1-hydroxycyclopropyl)carbonyl]piperidin-3-yl}-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

216)N-{(3R*,4S*)-4-{[(5-chloroindol-2-yl)carbonyl]amino}-[(1-methoxycyclopropyl)carbonyl]piperidin-3-yl}-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

217)7-chloro-N-((3R,4S)-1-(2-methoxyacetyl)-3-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}piperidin-4-yl)-3-isoquinolinecarboxamide

218)N¹-(4-chloro-3-fluorophenyl)-N²-((3R,4S)-1-(2-methoxyacetyl)-3-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}piperidin-4-yl)ethanediamide

219)N¹-(5-chloro-2-thienyl)-N²-((3R,4S)-1-(2-methoxyacetyl)-3-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}piperidin-4-yl)ethanediamide

220)N-{(1R,2S,5S)-2-{[2-(4-chlorophenoxy)acetyl]amino}-5-[(dimethylamino)carbonyl]cyclohexyl}-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

221)N-{(1R,2S,5S)-2-{[(6-chloro-4-oxo-4H-chromen-2-yl)carbonyl]amino}-5-[(dimethylamino)carbonyl]cyclohexyl}-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

222)7-chloro-N-((3R,4S)-1-(2-methoxyacetyl)-3-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}piperidin-4-yl)-3-cinnolinecarboxamide

223)N-((1R,2S,5S)-5-[(dimethylamino)carbonyl]-2-{[2-(4-fluoroanilino)-2-oxoethanethioyl]amino}cyclohexyl)-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

224)N-[(1R,2S,5S)-5-[(dimethylamino)carbonyl]-2-({2-[(5-fluoropyridin-2-yl)amino]-2-oxoethanethioyl}amino)cyclohexyl]-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

225)N-{(1R,2S,5S)-2-[({[(4-chlorophenyl)sulfonyl]amino}carbonyl)amino]-5-[(dimethylamino)carbonyl]cyclohexyl}-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

226)N¹-(5-chloropyridin-2-yl)-N²-((1S,2R,4S)-4-[(dimethylamino)carbonyl]-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)ethanediamide

227)N¹-(5-chloropyridin-2-yl)-N²-((1S,2R,4S)-4-[(dimethylamino)carbonyl]-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)ethanediamide

228)N¹-(5-chloropyridin-2-yl)-N²-((1S,2R,4S)-4-[(methylamino)carbonyl]-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)ethanediamide

229)N-{(1R,2S,5S)-5-[(dimethylamino)carbonyl]-2-({2-[(5-methylpyridin-2-yl)amino]-2-oxoethanethioyl}amino)cyclohexyl}-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

230)N-[(3R,4S)-4-{[2-(4-chloroanilino)-2-oxoethanethioyl]amino}-1-(2-methoxyacetyl)piperidin-3-yl]-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

231)N¹-(5-chloropyridin-2-yl)-N²-((1S,2R,4S)-4-[(dimethylamino)carbothioyl]-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)ethanediamide

232)N¹-(5-chloropyridin-2-yl)-N²-((3R,4S)-1-(2-methoxyethanethioyl)-3-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}piperidin-4-yl)ethanediamide

233)(1S,3R,4S)-4-({2-[(5-chloropyridin-2-yl)amino]-2-oxoacetyl}amino)-3-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexanecarboxylicacid 2,2,2-trichloroethyl ester

234)(1S,3R,4S)-4-({2-[(5-chloropyridin-2-yl)amino]-2-oxoacetyl}amino)-3-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexanecarboxylicacid

235)N-{(1R,2S,5S)-2-{[2-(4-chloroanilino)-1-methoxyimino-2-oxoethyl]amino}-5-[(dimethylamino)carbonyl]cyclohexyl}-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

236)N¹-((1S,2R,4S)-4-[(dimethylamino)carbonyl]-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)-N²-(5-ethynylpyridin-2-yl)ethanediamide

237)N-{(1R,2S,5S)-2-({2-[(6-chloropyridazin-3-yl)amino]-2-oxoethanethioyl}amino)-5-[(dimethylamino)carbonyl]cyclohexyl}-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

238)N-{(1R,2S,5S)-2-({2-[(6-chloropyridin-3-yl)amino]-2-oxoethanethioyl}amino)-5-[(dimethylamino)carbonyl]cyclohexyl}-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

239)N¹-((1S,2R,4S)-4-[(dimethylamino)carbonyl]-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)-N²-(5-methylpyridin-2-yl)ethanediamide

240)N¹-((1S,2R,4S)-4-[(dimethylamino)carbonyl]-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)-N²-(4-methylphenyl)ethanediamide

241)N¹-(5-chloropyridin-2-yl)-N²-((1S,2R,4S)-4-[(methylamino)carbothioyl]-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)ethanediamide

242)N-{(1R,2S,5S)-2-{[(4-chloroanilino)sulfonyl]amino}-5-[(dimethylamino)carbonyl]cyclohexyl}-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

243)N-{(1R,2S,5S)-2-({2-[(5-chloropyrimidin-2-yl)amino]-2-oxoethanethioyl}amino)-5-[(dimethylamino)carbonyl]cyclohexyl}-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

244)N-{(1R,2S,5S)-2-{[2-(4-chloro-3-nitroanilino)-2-oxoethanethioyl]amino}-5-[(dimethylamino)carbonyl]cyclohexyl}-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

245)N-{(1R,2S,5S)-2-{[2-(3-amino-4-chloroanilino)-2-oxoethanethioyl]amino}-5-[(dimethylamino)carbonyl]cyclohexyl}-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

246)N-{(1R,2S,5S)-2-{[(7-chlorocinnolin-3-yl)carbothioyl]amino}-5-[(dimethylamino)carbonyl]cyclohexyl}-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

247)N-{(1R,2S,5S)-2-({[(4-chlorobenzoyl)amino]carbonyl}amino)-5-[(dimethylamino)carbonyl]cyclohexyl}-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

248)N-{(1R,2S,5S)-2-{[(E)-3-(5-chloropyridin-2-yl)acryloyl]amino}-5-[(dimethylamino)carbonyl]cyclohexyl}-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

249)N-{(1R,2S,5S)-2-{[(Z)-3-(4-chlorophenyl)-2-fluoroacryloyl]amino}-5-[(dimethylamino)carbonyl]cyclohexyl}-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

250)N-{(1R,2S,5S)-2-({2-[(5-chloropyridin-2-yl)amino]-2-oxoethanethioyl}amino)-5-[(methylamino)carbonyl]cyclohexyl}-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

251)(3-{[((1S,2R,4S)-4-[(dimethylamino)carbonyl]-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)amino]carbonyl}phenyl)(imino)methylcarbamicacid tert-butyl ester

252)N-{(1R,2S,5S)-2-({3-[amino(imino)methyl]benzoyl}amino)-5-[(dimethylamino)carbonyl]cyclohexyl}-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

253)N-{(1R,2S,5S)-2-[(3-cyanobenzoyl)amino]-5-[(dimethylamino)carbonyl]cyclohexyl}-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

254)N-{(1R,2S,5S)-2-({3-[amino(hydroxyimino)methyl]benzoyl}amino)-5-[(dimethylamino)carbonyl]cyclohexyl}-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

255)(3-{[(1S,2R,4S)-4-[(dimethylamino)carbonyl]-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)amino]carbonyl}phenyl)(imino)methylcarbamicacid ethyl ester

256)N-[(1R,2S,5S)-5-[(dimethylamino)carbonyl]-2-({3-[imino(methylamino)methyl]benzoyl}amino)cyclohexyl]-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

257)N-{(1R,2S,5S)-2-({3-[amino(methoxyimino)methyl]benzoyl}amino)-5-[(dimethylamino)carbonyl]cyclohexyl}-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

258)N-{(1R,2S,5S)-2-{[(Z)-3-(5-chlorothien-2-yl)-2-fluoro-2-propenoyl]amino}-5-[(dimethylamino)carbonyl]cyclohexyl}-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

259)(1S,3R,4S)-4-({2-[(5-chloropyridin-2-yl)amino]-2-oxoethanethioyl}amino)-3-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexanecarboxylicacid tert-butyl ester

260)(1S,3R,4S)-4-({2-[(5-chloro-2-pyridinyl)amino]-2-oxoethanethioyl}amino)-3-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexanecarboxylicacid

261)N¹-(5-chloropyridin-2-yl)-N²-[(1S,2R,4R)-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}-4-(thiazol-2-yl)cyclohexyl]ethanediamide,N¹-(5-chloropyridin-2-yl)-N²-[(1S,2R,4S)-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}-4-(thiazol-2-yl)cyclohexyl]ethanediamide

262)N¹-(5-chloropyridin-2-yl)-N²-[(1S,2R,4S)-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}-4-(1,2,4-oxadiazol-3-yl)cyclohexyl]ethanediamide

263)N¹-(5-chloropyridin-2-yl)-N²-[(1S,2R,4S)-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}-4-(5-methyl-1,3,4-oxadiazol-2-yl)cyclohexyl]ethanediamide

264)N¹-(5-chloropyridin-2-yl)-N²-[(1S,2R,4S)-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}-4-(1,3,4-oxadiazol-2-yl)cyclohexyl]ethanediamide

265)N¹-(5-chloropyridin-2-yl)-N²-[(1S,2R,4S)-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}-4-(1,3-oxazol-2-yl)cyclohexyl]ethanediamide

266)N¹-(5-chloropyridin-2-yl)-N²-((1S,2R,4S)-4-(5-methyl-1,3,4-oxadiazol-2-yl)-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)ethanediamide

267)N¹-(5-chloropyridin-2-yl)-N²-[(1S,2R,4S)-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}-4-(1,3,4-thiadiazol-2-yl)cyclohexyl]ethanediamide

268)N-[(1R,2S,5S)-5-[(dimethylamino)carbonyl]-2-({2-[(5-fluoropyridin-2-yl)amino]-2-oxoethanethioyl}amino)cyclohexyl]-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

269)N-[(1R,2S,5S)-5-[(dimethylamino)carbonyl]-2-({2-[(5-fluoropyridin-2-yl)amino]-2-oxoethanethioyl}amino)cyclohexyl]-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

270)N¹-(5-chloropyridin-2-yl)-N²-[(1S,2R,4S)-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}-4-(5-methyl-1,3,4-thiadiazol-2-yl)cyclohexyl]ethanediamide

271)N¹-(5-chloropyridin-2-yl)-N²-[(1S,2R,4S)-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}-4-(1,3-oxazol-5-yl)cyclohexyl]ethanediamide

272)N¹-(5-chloropyridin-2-yl)-N²-((1S,2R,4S)-4-(5-methyl-1,2,4-oxadiazol-3-yl)-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)ethanediamide

273)N¹-(5-chloropyridin-2-yl)-N²-((1S,2R,4S)-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}-4-(4H-1,2,4-triazol-4-yl)cyclohexyl)ethanediamide

274)N¹-(5-chloro-2-thienyl)-N²-((1S,2R,4S)-4-(5-methyl-1,3,4-oxadiazol-2-yl)-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)ethanediamide

275)N¹-(5-bromo-2-pyridinyl)-N²-((1S,2R,4S)-4-(5-methyl-1,3,4-oxadiazol-2-yl)-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)ethanediamide

276)N¹-(4-chlorophenyl)-N²-((1S,2R,4S)-4-(5-methyl-1,3,4-oxadiazol-2-yl)-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)ethanediamide

277) N-[(1R,2S,5S)-2-{[(5-chloro-1H-indol-2-yl)carbonyl]amino}-5-(5-methyl-1,3,4-oxadiazol-2-yl)cyclohexyl]-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

278)N¹-((1S,2R,4S)-4-(5-methyl-1,3,4-oxadiazol-2-yl)-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)-N²-{5-[2-(trimethylsilyl)ethynyl]pyridin-2-yl}ethanediamide

279)N¹-(5-ethynylpyridin-2-yl)-N²-((1S,2R,4S)-4-(5-methyl-1,3,4-oxadiazol-2-yl)-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)ethanediamide

280)7-chloro-N-((1S,2R,4S)-4-(5-methyl-1,3,4-oxadiazol-2-yl)-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)-3-cinnolinecarboxamide

281)N-[(1R,2S,5S)-2-{[(Z)-3-(4-chlorophenyl)-2-fluoroacryloyl]amino}-5-(5-methyl-1,3,4-oxadiazol-2-yl)cyclohexyl]-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide

282)7-chloro-N-((1S,2R,4S)-4-(5-methyl-1,3,4-oxadiazol-2-yl)-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)-3-isoquinolinecarboxamide

283)6-chloro-N-((1S,2R,4S)-4-(5-methyl-1,3,4-oxadiazol-2-yl)-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)-4-oxo-1,4-dihydro-2-quinazolinecarboxamide

284)N¹-(5-chloropyridin-2-yl)-N²-[(1S,2R,4S)-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}-4-(1,2,4-oxadiazol-5-yl)cyclohexyl]ethanediamide

285)N¹-(5-chloropyridin-2-yl)-N²-{(1S,2R,4S)-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}-4-[5-(trifluoromethyl)-1,3,4-oxadiazol-2-yl]cyclohexyl}ethanediamide

286)N¹-(5-chloro-2-thienyl)-N²-((1S,2R,4S)-4-(3-methyl-1,2,4-oxadiazol-5-yl)-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)ethanediamide

287)N¹-(6-chloropyridazin-3-yl)-N²-((1S,2R,4S)-4-(3-methyl-1,2,4-oxadiazol-5-yl)-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)ethanediamide

288)N¹-(5-chloropyridin-2-yl)-N²-[(1S,2R,4S)-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}-4-(2-oxo-1,3-oxazolidin-3-yl)cyclohexyl]ethanediamide

289)N¹-(5-chloropyridin-2-yl)-N²-[(1S,2R,4S)-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}-4-(tetrazol-1-yl)cyclohexyl]ethanediamide

290)N¹-(5-chloropyridin-2-yl)-N²-[(1S,2R,4S)-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}-4-(1H-pyrrol-1-yl)cyclohexyl]ethanediamide

291)N¹-(5-chloropyridin-2-yl)-N²-[(1S,2R,4S)-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}-4-(1,2,4-triazol-5-yl)cyclohexyl]ethanediamide

292)N¹-(5-chloropyridin-2-yl)-N²-[(1S,2R,4S)-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}-4-(1-methyl-1H-1,2,4-triazol-5-yl)cyclohexyl]ethanediamide

293)7-chloro-N-((1S,2R,4S)-4-(3-methyl-1,2,4-oxadiazol-5-yl)-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)-3-cinnolinecarboxamide

294)N¹-(5-chloropyridin-2-yl)-N²-((3R,4S)-3-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}-1-(thiazol-2-yl)piperidin-4-yl)ethanediamide

Each of these compounds may be produced by use of the compound (5) as astarting material through a method described in Examples ofInternational Publication WO2004/058728 pamphlet.

Example

To further illustrate the present invention in greater detail, thefollowing examples will be given. However, it is to be understood thatthe present invention is not limited thereto.

Production Example 12-Cyano-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine hydrochloridemonohydrate

N,N-Dimethylacetamide (25 mL) was added to a mixture of copper cyanide(2.88 g) and sodium cyanide (1.58 g), and the resultant mixture washeated at 150° C. until all ingredients were completely dissolved, tothereby give a clear, colorless solution.2-Bromo-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine (5.00 g) wasadded to the solution, and the resultant mixture was stirred at 150° C.for 18 hours. The reaction mixture was allowed to cool to roomtemperature, and toluene and saturated aqueous sodium hydrogencarbonatewere added thereto. After any insoluble material was filtered off, thetoluene layer was separated from the aqueous layer, and the aqueouslayer was further extracted with toluene twice. The toluene layers werecombined, and the combined toluene layer was dried over sodium sulfateanhydrate. After any insoluble material was filtered off, the filtratewas concentrated under reduced pressure, and the concentrated residuewas dissolved in ethanol (35 mL). To the solution was added dropwise 1NHCl in ethanol (25 mL) at room temperature, to thereby form ahydrochloride salt, and the resultant mixture was stirred at 0° C. for 1hour. The precipitated crystals were collected by filtration, and werewashed with ethanol (20 mL). The thus-obtained wet crystal was dried atroom temperature under reduced pressure, to thereby give 3.05 g of thetitle compound.

¹H-NMR (D₂O) δppm: 4.72 (br, 2H), 3.77 (br, 2H), 3.36-3.29 (t, 2H, J=6.2Hz), 3.13 (s, 3H).

MS(FAB) m/z: 180 (M+H)⁺

Elementary analysis: as C₁₈H₁₂ClN₃OS,

Calculated: C, 41.11; H, 5.18; Cl, 15.17; N, 17.98; S, 13.72.

Found: C, 41.22; H, 4.99; Cl, 15.26; N, 17.95; S, 13.69.

Production Example 22-Cyano-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine

A solution of sodium hydrogencarbonate (272.33 mg) in water (5 mL) wasadded to 2-cyano-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridinehydrochloride monohydrate (500.30 mg) at room temperature, and after allingredients were completely dissolved, the resultant solution wasextracted with toluene three times (10 mL×3). The toluene layers werecombined, and the combined toluene layer was dried over sodium sulfateanhydrate (2.00 g). After any insoluble material was filtered off, thefiltrate was concentrated at 40° C. under reduced pressure, to therebygive 384.28 mg of the title compound.

¹H-NMR(CDCl₃) δppm: 3.76-3.73 (t, 2H, J=1.5 Hz), 3.03-2.98 (dt, 2H,J=1.5, 5.9 Hz), 2.89-2.84 (t, 2H, J=5.9 Hz), 2.52 (s, 3H).

MS(FAB) m/z: 180 (M+H)⁺

Elementary analysis: as C₈H₉N₃S,

Calculated: C, 53.61; H, 5.06; N, 23.44; S, 17.89.

Found: C, 53.40; H, 5.08; N, 23.41; S, 17.89.

Production Example 35-Methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxylic acidhydrochloride

To 2-cyano-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridinehydrochloride monohydrate (500.61 mg) were added ethanol (5 mL) and 4Naqueous lithium hydroxide (1.34 mL) at room temperature, and theresultant mixture was stirred at 50° C. for 7 hours. After the reactionmixture was cooled with ice-water, 1N HCl in ethanol (7.5 mL) was addedthereto, to thereby form a hydrochloride salt, followed by stirring atthe same temperature for 1.5 hours. The precipitated crystals werecollected by filtration, and were washed with ethanol (2 mL). The wetcrystal was dried at room temperature under reduced pressure, to therebygive 466.98 mg of the title compound.

¹H-NMR (D₂O) δppm: 4.82-4.88 (d, 1H, J=16.0 Hz), 4.51-4.57 (d, 1H,J=16.0 Hz), 3.88-3.96 (m, 1H), 3.60-3.70 (m, 1H), 3.22-3.33 (m, 2H),3.15 (s, 3H).

MS(EI) m/z: 198 (M)⁺

Elementary analysis: as C₈H₁₁ClN₂O₂S,

Calculated: C, 40.94; H, 4.72; Cl, 15.11; N, 11.94; S, 13.66.

Found: C, 40.50; H, 4.66; Cl, 15.31; N, 11.97; S, 13.68.

Production Example 45-Methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxylic acidhydrochloride

To 2-cyano-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine (199.30mg) were added ethanol (2 mL) and 4N aqueous lithium hydroxide (0.42 mL)at room temperature, and the mixture was stirred at 50° C. for 10 hours.The reaction mixture was cooled with ice-water, and 1N HCl in ethanol(2.8 mL) was added thereto, to thereby form a hydrochloride salt. Theprecipitated crystals were collected by filtration, and were washed withethanol (1 mL). The wet matter was dried at room temperature underreduced pressure, to thereby give 215.37 mg of the title compound.

¹H-NMR (D₂O) δppm: 4.82-4.88 (d, 1H, J=16.0 Hz), 4.51-4.57 (d, 1H,J=16.0 Hz), 3.88-3.96 (m, 1H), 3.60-3.70 (m, 1H), 3.22-3.33 (m, 2H),3.15 (s, 3H).

MS(EI) m/z: 198 (M)⁺

Production Example 5 5-Methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine

2-Amino-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine (10.00 g) wasdissolved in a mixture of sulfuric acid (25 mL), hypophosphorous acid(50%, 13 mL), and water (100 mL) at 15 to 18° C., to thereby give anorange solution. To the solution was added dropwise a solution of sodiumnitrite (8.15 g) in water (30 mL) at −2 to 3° C. over 30 minutes. Afterthe resultant mixture was stirred at 0 to 10° C. for 2.5 hours, 8Naqueous potassium hydroxide (130 mL) was added dropwise thereto, and thepH was found to be 12.6. The precipitated potassium sulfate was filteredoff, and was washed with ethyl acetate (200 mL). The aqueous layer wasseparated from the filtrate, and was further extracted with ethylacetate twice (200 mL×2). The organic layers were combined, and thecombined organic layer was dried over sodium sulfate anhydrate (30.00g). After any insoluble material was filtered off and washed with ethylacetate (100 mL), the filtrate was concentrated under reduced pressure,to thereby give 6.15 g of the title compound.

¹H-NMR (CDCl₃) δppm: 8.62 (s, 1H), 3.71-3.67 (t, 2H, J=1.7 Hz),3.01-2.95 (dt, 2H, J=1.7 Hz, 5.9 Hz), 2.84-2.80 (t, 2H, J=5.9 Hz), 2.51(s, 3H).

Production Example 6 5-Methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridinep-toluenesulfonic acid salt

5-Methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine (1.00 g) wasdissolved in 2-propanol (10 mL) at room temperature, andp-toluenesulfonic acid monohydrate (1.23 g) was added thereto at roomtemperature, followed by stirring at room temperature for 20 minutes.When the resultant mixture was cooled to 0° C., a salt was crystallizedout of the mixture. After the resultant mixture was stirred at 0° C. for2 hours, the precipitated salt was collected by filtration, and waswashed with 2-propanol (2 mmol). The wet material was dried at roomtemperature under reduced pressure, to thereby give 1.91 g of the titlecompound.

¹H-NMR (D₂O) δppm: 9.00 (s, 1H), 7.68-7.65 (d, 2H, J=8.1 Hz), 7.35-7.32(d, 2H, J=8.1 Hz), 4.25-4.85 (br, 2H), 3.40-3.95 (br, 2H), 3.25-3.18 (t,2H, J=6.0 Hz), 3.08 (s, 3H), 2.38 (s, 3H).

MS(EI) m/z: 154 (M)⁺

Elementary analysis: as C₁₄H₁₈N₂O₃S₂.

Calculated: C, 51.51; H, 5.56; N, 8.58; S, 19.65.

Found: C, 51.24; H, 5.52; N, 8.81; S, 19.37.

Production Example 75-Methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxylic acidhydrochloride

5-Methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine (1.00 g) wasdissolved in toluene (10 mL) at room temperature, and triethylamine(1.81 mL) and trichloroacetyl chloride (1.45 mL) were sequentially addedthereto at room temperature, followed by stirring at room temperaturefor 4 hours. To the resultant mixture was added a solution of lithiumhydroxide monohydrate (1.22 g) in water (10 mL), to thereby performhydrolysis. The organic layer was separated from the aqueous layer, andwas further extracted with water (10 mL). The aqueous layers werecombined, and the combined aqueous layer was concentrated in a bath at50° C. under reduced pressure. Ethanol (10 mL) was added thereto, andthe resultant mixture was again concentrated under reduced pressure.Ethanol (15 mL) was added to the concentrated residue, and the resultantmixture was cooled with ice-water. Concentrated hydrochloric acid (2.7mL) was added dropwise thereto, to thereby form a hydrochloride salt,and the resultant mixture was stirred at the same temperature for 1.5hours. The precipitated crystals were collected by filtration, and werewashed with ethanol (4 mL). The wet matter was dried at room temperatureunder reduced pressure, to thereby give 1.25 g of the title compound.

¹H-NMR (D₂O) δppm: 4.82-4.88 (d, 1H, J=16.0 Hz), 4.51-4.57 (d, 1H,J=16.0 Hz), 3.88-3.96 (m, 1H), 3.60-3.70 (m, 1H), 3.22-3.33 (m, 2H),3.15 (s, 3H)

MS(FAB) m/z: 199 (M+H)⁺

Production Example 82-Amino-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine

A solution of 1-methyl-4-piperidone (180.0 g) in 2-propanol (1.44 L) washeated to 50° C., and to the solution were sequentially added a solutionof cyanamide (67.0 g) in 2-propanol (360 mL) and sulfur powder (51.0 g).After a catalytic amount of pyrrolidine (13.3 mL) was added thereto, theresultant mixture was stirred at or above 50° C. for 2 hours, and wasallowed to cool to room temperature, followed by stirring overnight. Theresultant mixture was cooled to or below 10° C. in an ice-water bath,and was stirred for 1 hour at the same temperature. The precipitatedcrystals were collected by filtration, and were washed with 2-propanol(540 mL). The wet crystal was dried at 40° C. under reduced pressure, tothereby give 209.9 g of the title compound.

¹H-NMR (CDCl₃) δppm: 4.86 (br, 2H), 3.47-3.46 (t, 2H, J=1.9 Hz),2.78-2.71 (m, 2H), 2.71-2.65 (m, 2H), 2.47 (s, 3H).

MS(FAB) m/z: 170 (M+H)⁺

Elementary analysis: as C₇H₁₁N₃S.

Calculated: C, 49.68; H, 6.55; N, 24.83; S, 18.95.

Found: C, 49.70; H, 6.39; N, 24.91; S, 19.00.

Production Example 92-Amino-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridinedihydrobromide

1-Methyl-4-piperidone (100.0 g) was dissolved in 2-propanol (800 mL) atroom temperature, and the solution was heated to an internal temperatureof 50° C. in a water bath. To the resultant mixture were sequentiallyadded a solution of cyanamide (37.16 g) in 2-propanol (200 mL) andsulfur powder (28.34 g) at 50° C. A catalytic amount of pyrrolidine (7.4mL) was added thereto, and the resultant mixture was stirred at 50 to64° C. for 1 hour. After the resultant mixture was allowed to cool toroom temperature, 48% hydrobromic acid (358.0 g) was added dropwisethereto at 30 to 40° C., and the mixture was cooled to or below 10° C.in an ice-water bath, followed by stirring at the same temperature for1.5 hours. The precipitated crystals were collected by filtration, andwere washed with 2-propanol (500 mL). The wet crystal was dried at 40°C. under reduced pressure, to thereby give 258.2 g of the titlecompound.

¹H-NMR (D₂O) δppm: 4.45-4.53 (d, 1H, J=15.2 Hz), 4.20-4.26 (d, 1H,J=15.2 Hz), 3.75-3.90 (m, 1H), 3.50-3.67 (m, 1H), 3.10 (s, 3H),2.91-3.18 (m, 2H).

Elementary analysis: as C₇H₁₃Br₂N₃S.

Calculated: C, 25.39; H, 3.96; Br, 48.27; N, 12.69; S, 9.69.

Found: C, 25.54; H, 3.93; Br, 48.09; N, 12.62; S, 9.72.

Production Example 102-Bromo-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine

2-Amino-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine (600.0 g) wassuspended in water (6.0 L), and 48% hydrobromic acid (4.2 L) was addeddropwise thereto at 5 to 15° C. A solution of sodium nitrite (367.2 g)in water (1.8 L) was added dropwise thereto at 0 to 5° C. over 1.5hours, and the reaction mixture was heated to 30° C., followed bystirring for 24 hours. The resultant mixture was made strongly basic (pH12.5) with 5N aqueous sodium hydroxide (6.0 L). The aqueous layer wasextracted with toluene twice (12.0 L, 6.0 L), and the toluene layerswere combined. The combined toluene layer was dried over sodium sulfateanhydrate (1202.0 g), and after any insoluble material was filtered off,the mother liquor was concentrated at 40° C. under reduced pressure, tothereby give 557.6 g of the title compound.

¹H-NMR (CDCl₃) δppm: 3.58-3.57 (t, 3H, J=1.8 Hz), 2.92-2.87 (m, 2H),2.81-2.76 (m, 2H), 2.49 (s, 3H).

Production Example 112-Bromo-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridinep-toluenesulfonic acid salt

2-Bromo-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine (557.6 g) wasdissolved in methanol (3.9 L), and to the solution was added dropwise asolution of p-toluenesulfonic acid monohydrate (500.0 g) in methanol(1.7 L) at 30° C. The resultant mixture was stirred at the sametemperature for 1 hour, and then at or below 10° C. for 2 hours. Theprecipitated crystals were collected by filtration, and were washed withmethanol (1.1 L), followed by drying at 40° C. under reduced pressure,to thereby give 851.9 g of the title compound.

¹H-NMR (DMSO-d₆) δppm: 10.15 (br, 1H), 7.47-7.43 (d, 2H, J=8.2 Hz),7.09-7.07 (d, 2H, J=8.2 Hz), 4.47 (s, 2H), 3.58 (s, 2H) 3.04 (t, 2H,J=6.1 Hz), 2.96 (s, 3H), 2.29 (s, 3H).

Elementary analysis: as C₁₄H₁₇BrN₂O₃S₂.

Calculated: C, 41.48; H, 4.23; Br, 19.71; N, 6.91; S, 15.82.

Found: C, 41.52; H, 4.33; Br, 19.80; N, 6.99; S, 15.90.

Production Example 122-Bromo-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridinep-toluenesulfonic acid salt

2-Amino-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridinedihydrobromide (50.01 g) was suspended in a mixture of water (250 mL)and 48% hydrobromic acid (175 mL) at room temperature. After thesuspension was cooled to an internal temperature of 10° C. or lower, asolution of sodium nitrite (15.63 g) in water (75 mL) was added dropwisethereto over 1.5 hours while the internal temperature was kept at orbelow 10° C. After the resultant mixture was stirred at or below 10° C.for 20 hours, 10N aqueous sodium hydroxide (175 mL) was added dropwisethereto while being kept at or below 20° C., to thereby make thesolution basic, and the pH of the resultant solution was found to be13.1. Subsequently, the aqueous layer was extracted with toluene twice(375 mL, 250 mL), and the toluene layers were combined. A quarter of theamount of the combined toluene layer was used for the followingprocedures. The toluene layer was concentrated, and the concentratedresidue was dissolved in methanol (43.8 mL). A solution ofp-toluenesulfonic acid monohydrate (5.03 g) in methanol (18.8 mL) wasadded dropwise thereto at room temperature, and the mixture was cooledto or below 10° C., followed by stirring at the same temperature for 1.5hours. The precipitated crystals were collected by filtration, and werewashed with methanol (18.8 mL). The wet crystal was dried at 40° C.under reduced pressure, to thereby give 9.05 g of the title compound.

¹H-NMR (DMSO-d₆) δppm: 10.15 (br, 1H), 7.47-7.43 (d, 2H, J=8.2 Hz),7.09-7.07 (d, 2H, J=8.2 Hz), 4.47 (s, 2H), 3.58 (s, 2H), 3.04 (t, 2H,J=6.1 Hz), 2.96 (s, 3H), 2.29 (s, 3H).

Elementary analysis: as C₁₄H₁₇BrN₂O₃S₂.

Calculated: C, 41.48; H, 4.23; Br, 19.71; N, 6.91; S, 15.82.

Found: C, 41.54; H, 4.18; Br, 19.83; N, 7.03; S, 16.02.

Production Example 13 Lithium5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxylate

To 2-bromo-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridinep-toluenesulfonic acid salt (490.0 g) was added 2N aqueous sodiumhydroxide (2.45 L), and the mixture was stirred at room temperature for30 minutes. The resultant mixture was extracted with toluene twice (4.9L×2), and the organic layer was dried over sodium sulfate anhydrate(979.8 g). After any insoluble material was filtered off, the motherliquor was concentrated at or below 40° C. under reduced pressure, tothereby give 2-bromo-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine(284.0 g) as a brown oily compound. The resultant2-bromo-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine (284.0 g) wasdissolved in anhydrous tetrahydrofuran (2.84 L). After the system waspurged with argon, n-Butyllithium (as 1.59 mol/L n-hexane solution, 766mL) was added dropwise to the solution at −40 to −30° C., and theresultant mixture was stirred at the same temperature for 1 hour. Afterpassing carbon dioxide gas through the reaction mixture at −40 to −25°C., the mixture was stirred under carbon dioxide atmosphere at the sametemperature for 1 hour. The resultant mixture was heated to roomtemperature, and ethyl acetate (1.42 L) was added thereto. Theprecipitated solid was filtered off, and was washed with ethyl acetate(0.85 L). The thus-obtained solid material was dried at 40° C. underreduced pressure, and was pulverized, to thereby give 235.1 g of thetitle compound.

¹H-NMR (DMSO-d₆) δppm: 3.54 (s, 2H), 2.65-2.85 (m, 4H), 2.36 (s, 3H).

Production Example 145-Methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxylic acidhydrochloride

To lithium5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxylate (3.00g) was added 1N HCl in ethanol (36 mL), and the mixture was stirred atroom temperature for 1 hour. The precipitated crystals were collected byfiltration, and were washed with ethanol (9 mL). The wet crystal wasdried at room temperature under reduced pressure, to thereby give 2.76 gof the title compound.

¹H-NMR (D₂O) δppm: 4.82-4.88 (d, 1H, J=16.0 Hz), 4.51-4.57 (d, 1H,J=16.0 Hz), 3.88-3.96 (m, 1H), 3.60-3.70 (m, 1H), 3.22-3.33 (m, 2H),3.15 (s, 3H).

Elementary analysis: as C₈H₁₁ClN₂O₂S.

Calculated: C, 40.94; H, 4.72; N, 11.94; S, 13.66.

Found: C, 40.51; H, 4.65; N, 11.79; S, 13.53.

Production Example 155-Methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxylic acidhydrochloride

2-Bromo-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridinep-toluenesulfonic acid salt (40.00 g) was mixed with 1N aqueous sodiumhydroxide (200 mL) at room temperature, and the mixture was stirred for30 minutes. The aqueous layer was extracted with toluene twice (400mL×2), and the organic layers were combined. The combined organic layerwas washed with 5% brine (200 mL), and was concentrated to 80 mL at anexternal temperature of 50° C. or lower under reduced pressure. A samplefor water content measurement was taken from the resultant mixture(weight of the mixture after concentration: 91.03 g, weight of themixture after sampling: 87.68 g). The sample of the concentrated mixturewas subjected to water content measurement with Karl-Fischer MoistureTitrator, and the water content was found to be 0.0231% (on aweight-to-weight ratio). The remaining portion of the concentratedmixture after sampling was dissolved in anhydrous tetrahydrofuran (231mL). After the system was purged with argon, the reaction mixture wascooled to an internal temperature of −30° C. or lower, and to thesolution was added dropwise n-butyllithium (as 1.59 mol/L n-hexanesolution, 61.7 mL) while the internal temperature was kept at or below−30° C., followed by stirring at the same temperature for 1 hour. Afterpassing carbon dioxide gas through the resultant mixture while theinternal temperature was kept at or below −30° C., the reaction mixturewas stirred under carbon dioxide atmosphere for 1 hour. The resultantmixture was heated to an internal temperature of 15° C., and methanol(193 mL) was added thereto, to thereby dissolve the precipitated solid,and concentrated hydrochloric acid (19.3 mL) was added dropwise theretowhile the internal temperature was kept at or below 20° C. The resultantmixture was cooled to an internal temperature of 10° C. or lower, andwas stirred at the same temperature for 1 hour. The precipitatedcrystals were collected by filtration, and were washed with methanol (58mL). The wet crystal was dried at room temperature under reducedpressure, to thereby give 21.20 g of the title compound.

¹H-NMR (D₂O) δppm: 4.82-4.88 (d, 1H, J=16.0 Hz), 4.51-4.57 (d, 1H,J=16.0 Hz), 3.88-3.96 (m, 1H), 3.60-3.70 (m, 1H), 3.22-3.33 (m, 2H),3.15 (s, 3H).

MS(EI) m/z: 198 (M)⁺

Elementary analysis: as C₈H₁₁ClN₂O₂S.

Calculated: C, 40.94; H, 4.72; Cl, 15.11; N, 11.94; S, 13.66.

Found: C, 40.83; H, 4.56; Cl, 14.81; N, 11.91; S, 13.87.

Production Example 16N¹-(5-Chloropyridin-2-yl)-N²-((1S,2R,4S)-4-[(dimethylamino)carbonyl]-2-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl)ethanediamide

N¹-{(1S,2R,4S)-2-Amino-4-[(dimethylamino)carbonyl]cyclohexyl}-N²-(5-chloropyridin-2-yl)ethanediamide(553.4 mg) was dissolved in dimethylacetamide (7 mL), and to thesolution were added 1-hydroxybenzotriazole monohydrate (245.1 mg),5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxylic acidhydrochloride (386.0 mg), and1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (345.0 mg)at room temperature. The resultant mixture was stirred for 13 hours, andtriethylamine and water were added thereto. The precipitated crystalswere collected by filtration, and were dried, to thereby give 674.1 mgof the title compound.

¹H-NMR(CDCl₃) δppm: 1.60-1.98 (3H, m), 2.00-2.16 (3H, m), 2.52 (3H, s),2.78-2.90 (3H, m), 2.92-2.98 (2H, m), 2.95 (3H, s), 3.06 (3H, s), 3.69(1H, d, J=15.4 Hz), 3.75 (1H, d, J=15.4 Hz), 4.07-4.15 (1H, m),4.66-4.72 (1H, m), 7.40 (1H, d, J=8.8, 0.6 Hz), 7.68 (1H, dd, J=8.8, 2.4Hz), 8.03 (1H, d, J=7.8 Hz), 8.16 (1H, dd, J=8.8, 0.6 Hz), 8.30 (1H, dd,J=2.4, 0.6 Hz), 9.72 (1H, s).

MS(ESI) m/z: 548 (M+H)⁺.

1. A process for producing5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxylic acid offormula (5) or a salt thereof, comprising:

reacting 2-bromo-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine offormula (3) or a salt thereof,

with a metal cyanide, to obtain2-cyano-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine of formula(4) or a salt thereof,

and hydrolyzing the2-cyano-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine of formula(4) or a salt thereof.
 2. The process according to claim 1, wherein themetal cyanide is a mixture of sodium cyanide and copper cyanide.
 3. Theprocess according to claim 1, wherein the hydrolysis of the2-cyano-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine of formula(4) or a salt thereof, comprises treatment with an aqueous solution ofan alkali metal hydroxide.
 4. The process according to claim 3, whereinthe alkali metal hydroxide is lithium hydroxide.